Capture in ventricle-from-atrium cardiac therapy

ABSTRACT

Ventricle-from-atrium (VfA) cardiac therapy may utilize a tissue-piercing electrode implanted in the left ventricular myocardium of the patient&#39;s heart from the right atrium through the right atrial endocardium and central fibrous body. The exemplary devices and methods may determine whether the tissue-piercing electrode is achieving effective left ventricular capture. Additionally, one or more pacing parameters, or paced settings, may be adjusted in view of the effective left ventricular capture determination.

The present application claims the benefit of U.S. ProvisionalApplication Ser. No. 62/736,905, filed Sep. 26, 2018, which isincorporated by reference herein in its entirety.

The present disclosure is generally related to medical implantabledevices and methods for ventricle-from-atrium (VfA) cardiac therapy.More specifically, the devices and methods relate to left ventricularcapture using VfA cardiac therapy.

The cardiac conduction system includes the sinus atrial (SA) node, theatrioventricular (AV) node, the bundle of His, bundle branches andPurkinje fibers. A heart beat is initiated in the SA node, which may bedescribed as the natural “pacemaker” of the heart. An electrical impulsearising from the SA node causes the atrial myocardium to contract. Theelectrical impulse, or electrical pulse or signal, is conducted to theventricles via the AV node which inherently delays the conduction toallow the atria to stop contracting before the ventricles begincontracting thereby providing proper AV synchrony. The electricalimpulse is conducted from the AV node to the ventricular myocardium viathe bundle of His, bundle branches, and Purkinje fibers.

Patients with a conduction system abnormality, such as poor AV nodeconduction or poor SA node function, may receive an implantable medicaldevice (IMD), such as a pacemaker, to restore a more normal heart rhythmand AV synchrony. Some types of IMDs, such as cardiac pacemakers,implantable cardioverter defibrillators (ICDs), or cardiacresynchronization therapy (CRT) devices, provide therapeutic electricalstimulation to a heart of a patient via electrodes on one or moreimplantable endocardial, epicardial, or coronary venous leads that arepositioned in or adjacent to the heart. The therapeutic electricalstimulation may be delivered to the heart in the form of pulses orshocks for pacing, cardioversion, or defibrillation. In some cases, anIMD may sense intrinsic depolarizations of the heart, and control thedelivery of therapeutic stimulation to the heart based on the sensing.

Delivery of therapeutic electrical stimulation to the heart can beuseful in addressing cardiac conditions such as ventricular dyssynchronythat may occur in patients. Ventricular dyssynchrony may be described asa lack of synchrony or a difference in the timing of contractions in theright and left ventricles of the heart. Significant differences intiming of contractions can reduce cardiac efficiency. CRT, delivered byan IMD to the heart, may enhance cardiac output by resynchronizing theelectromechanical activity of the ventricles of the heart. CRT mayinclude “triple chamber pacing” when pacing the right atrium, rightventricle, and left ventricle.

Cardiac arrhythmias may be treated by delivering electrical shocktherapy for cardioverting or defibrillating the heart in addition tocardiac pacing, for example, from an ICD, which may sense a patient'sheart rhythm and classify the rhythm according to an arrhythmiadetection scheme in order to detect episodes of tachycardia orfibrillation. Arrhythmias detected may include ventricular tachycardia(VT), fast ventricular tachycardia (FVT), ventricular fibrillation (VF),atrial tachycardia (AT) and atrial fibrillation (AT). Anti-tachycardiapacing (ATP) can be used to treat ventricular tachycardia (VT) tosubstantially terminate many monomorphic fast rhythms.

Dual chamber medical devices are available that include a transvenousatrial lead carrying electrodes that may be placed in the right atriumand a transvenous ventricular lead carrying electrodes that may beplaced in the right ventricle via the right atrium. The dual chambermedical device itself is generally implanted in a subcutaneous pocketand the transvenous leads are tunneled to the subcutaneous pocket. Adual chamber medical device may sense atrial electrical signals andventricular electrical signals and can provide both atrial pacing andventricular pacing as needed to promote a normal heart rhythm and AVsynchrony. Some dual chamber medical devices can treat both atrial andventricular arrhythmias.

Intracardiac medical devices, such as a leadless pacemaker, have beenintroduced or proposed for implantation entirely within a patient'sheart, eliminating the need for transvenous leads. A leadless pacemakermay include one or more electrodes on its outer housing to delivertherapeutic electrical signals and/or sense intrinsic depolarizations ofthe heart. Intracardiac medical devices may provide cardiac therapyfunctionality, such as sensing and pacing, within a single chamber ofthe patient's heart. Single chamber intracardiac devices may also treateither atrial or ventricular arrhythmias or fibrillation. Some leadlesspacemakers are not intracardiac and may be positioned outside of theheart and, in some examples, may be anchored to a wall of the heart viaa fixation mechanism.

In some patients, single chamber devices may adequately address thepatient's needs. However, single chamber devices capable of only singlechamber sensing and therapy may not fully address cardiac conductiondisease or abnormalities in all patients, for example, those with someforms of AV dyssynchrony or tachycardia. Dual chamber sensing and/orpacing functions, in addition to ICD functionality in some cases, may beused to restore more normal heart rhythms.

SUMMARY

The techniques, methods, and processes of this disclosure generallyrelate to implantable medical devices, systems, and methods forventricle-from-atrium (VfA) cardiac resynchronization therapy (CRT).Additionally, techniques, methods, and processes of this disclosure maybe applied, or used with, cardiac therapy, including single chamber ormultiple chamber pacing (e.g., dual or triple chamber pacing),atrioventricular synchronous pacing, asynchronous pacing, triggeredpacing, or tachycardia-related therapy.

A VfA device may be implanted in the right atrium (RA) with atissue-piercing electrode extending from the right atrium into the leftventricular myocardium. The tissue-piercing electrode may be used todeliver pacing therapy to the left ventricular for various cardiactherapies. To determine whether the pacing has captured the leftventricle and/or whether the pacing is effective, electrical activitymay be measured, or other physiological response measurements may betaken, following a left ventricular pace. The electrical activity andother physiological response measurements may be evaluated (e.g.,compared to various thresholds, etc.) to determine whether the pacingtherapy has effectively captured the left ventricle.

Additionally, if the ventricular pacing therapy is determined to beineffective or not having captured the left ventricle, the ventricularpacing therapy may be adjusted until the ventricular pacing therapy ismade to be effectively capturing the left ventricle. For example, one ormore paced settings may be adjusted, or modified, and the electricalactivity or other physiological information may be monitored. Themonitored electrical activity or other physiological information mayagain be evaluated to determine whether the ventricular pacing therapyhas now effectively captured the left ventricle. For example, theatrioventricular (A-V) pacing delay may be adjusted until leftventricular capture is determined. Advantageously, in one or moreembodiments, the techniques of this disclosure may be used to calibrateor deliver more optimal pacing therapy without using monitoredelectrical activity of the right ventricle of the patient's heart.

In other words, this disclosure describes methods of monitoringeffectiveness of ventricular capture and modifying one or more therapyparameters in context of a leadless VfA pacing device that is implantedin the AV septal area with electrodes that can sense/pace the atrium aswell as the ventricle, especially the left ventricle forresynchronization pacing.

One illustrative implantable medical device may include a plurality ofelectrodes. The plurality of electrodes may include a tissue-piercingelectrode implantable from the triangle of Koch region of the rightatrium through the right atrial endocardium and central fibrous body todeliver cardiac therapy to or sense electrical activity of the leftventricle in the basal and/or septal region of the left ventricularmyocardium of a patient's heart, and a right atrial electrodepositionable within the right atrium to deliver cardiac therapy to orsense electrical activity of the right atrium of the patient's heart.The illustrative implantable medical device may further include atherapy delivery circuit operably coupled to the plurality of electrodesto deliver cardiac therapy to the patient's heart, a sensing circuitoperably coupled to the plurality of electrodes to sense electricalactivity of the patient's heart, and a controller comprising processingcircuitry operably coupled to the therapy delivery circuit and thesensing circuit. The controller may be configured to monitoreffectiveness of left ventricular capture. Monitoring effectiveness ofleft ventricular capture may include delivering a left ventricular paceusing the tissue-piercing electrode, monitoring electrical activity ofthe left ventricle using the tissue-piercing electrode following theleft ventricular pace, and determining effectiveness of left ventriculartissue capture of the left ventricular pace based on the monitoredelectrical activity.

One illustrative method may include providing a tissue-piercingelectrode implanted from the triangle of Koch region of the right atriumthrough the right atrial endocardium and central fibrous body to delivercardiac therapy to or sense electrical activity of the left ventricle inthe basal and/or septal region of the left ventricular myocardium of apatient's heart and providing a right atrial electrode positionablewithin the right atrium to deliver cardiac therapy to or senseelectrical activity of the right atrium of the patient's heart. Theillustrative method may further include delivering a left ventricularpace using the tissue-piercing electrode, monitoring electrical activityof the left ventricle using the tissue-piercing electrode following theleft ventricular pace, and determining effectiveness of left ventriculartissue capture of the left ventricular pace based on the monitoredelectrical activity.

One illustrative implantable medical device may include a plurality ofelectrodes, the plurality of electrodes including at least atissue-piercing electrode implantable from the triangle of Koch regionof the right atrium through the right atrial endocardium and centralfibrous body to deliver cardiac therapy to or sense electrical activityof the left ventricle in the basal and/or septal region of the leftventricular myocardium of a patient's heart and a right atrial electrodepositionable within the right atrium to deliver cardiac therapy to orsense electrical activity of the right atrium of the patient's heart.The illustrative implantable medical device may further include atherapy delivery circuit operably coupled to the plurality of electrodesto deliver cardiac therapy to the patient's heart, a sensing circuitoperably coupled to the plurality of electrodes to sense electricalactivity of the patient's heart, and a controller comprising processingcircuitry operably coupled to the therapy delivery circuit and thesensing circuit. The controller may be further configured to deliver aleft ventricular pace therapy using the tissue-piercing electrode,monitor effectiveness of left ventricular capture over a plurality ofcardiac cycles based on electrical activated monitored using at leastthe tissue-piercing electrode, determine that effective left ventricularcapture is not occurring based on the monitored of effectiveness of leftventricular capture over the plurality of cardiac cycles, and adjustleft ventricular pacing in response to determination that effective leftventricular capture is not occurring.

One exemplary VfA device is a leadless pace/sense device for deliveringAV synchronous ventricular sensing therapy. The device may be implantedin the AV septal area with sense/pace cathodes (e.g., an atrial cathode)in the atrium and sense/pace cathodes (e.g., a ventricular cathode) inthe ventricle and a third electrode as a common anode. During deliveryof ventricular pacing from such a device, effectiveness of therapy maybe monitored based on analyzing morphologic features of a near-fieldpaced electrogram (e.g., the ventricular cathode to the atrial anode)based on the following criteria: (1) absolute amplitude of electrogrambaseline<a threshold in millivolts; (2) the minimum negative deflectionwithin a certain time window from the paced event is more negative thana certain threshold in millivolts; and (3) the timing of the negativeminimum measured relative to the timing of the paced event is less thana certain interval in milliseconds. If all of the above three criteriais met, effective tissue capture may be determined to occur for thatparticular ventricular pace and a diagnostic for effective ventricularpacing may be provided for such a VfA device.

The exemplary devices may also do continuous therapy adjustments basedon indication of effective or ineffective pacing. For example, if pacingis ineffective for at least X out of Y beats, the device may run aseries of diagnostic tests to correct it. If in DDD(R) mode, the devicemay initiate a capture test to measure capture thresholds and re-setoutputs based on a certain value above the capture threshold. If pacingcontinues to be ineffective for X out of Y beats, the device maydecrement AV delays for pacing in certain steps and continue to monitorthe degree of effectiveness. There may be a lower bound (e.g., 60milliseconds for intrinsic atrial sensing and 70 milliseconds for atrialpacing) to the AV delay beyond which it would not be furtherdecremented. If in VVI (R)mode, and the device gets at least X out Yineffective pacing beats and at least W out of Y sense beats, it mayincrease the heart rate and continue to monitor effectiveness ofcapture. The increment in heart rate may be modified up to a certainmaximum rate (e.g., 130 beats per minute) while in VVI mode. If in VVImode, the device determines at least X out of Y ineffective pacing beatsbut no sensed beats, it may initiate a capture threshold test toestablish capture thresholds and reset pacing outputs. The exemplarydevices may continue to track proportion of effective pacing and issuean alert if the effective pacing falls below a certain degree.

The details of one or more aspects of the disclosure are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the techniques described in this disclosurewill be apparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a conceptual diagram of an illustrative cardiac therapy systemincluding an intracardiac medical device implanted in a patient's heartand a separate medical device positioned outside of the patient's heartfor use with, e.g., the illustrative methods of FIGS. 16-18.

FIGS. 2-4 are conceptual diagrams of illustrative cardiac therapysystems including medical devices including leads with electrodesimplanted in a patient's heart for use with, e.g., the illustrativemethods of FIGS. 16-18.

FIG. 5 is an enlarged conceptual diagram of the intracardiac medicaldevice of FIG. 1 and anatomical structures of the patient's heart.

FIG. 6 is a conceptual diagram of a map of a patient's heart in astandard 17 segment view of the left ventricle showing various electrodeimplantation locations for use with, e.g., the exemplary system anddevices of FIGS. 1-4.

FIG. 7 is a perspective view of an intracardiac medical device having adistal fixation and electrode assembly that includes a distalhousing-based electrode implemented as a ring electrode for use with,e.g., the illustrative systems and devices of FIGS. 1-4.

FIG. 8 is a block diagram of illustrative circuitry that may be enclosedwithin the housing of the medical devices of FIGS. 1-4, for example, toprovide the functionality and therapy described herein.

FIG. 9 is a perspective view of another illustrative intracardiacmedical device for use with, e.g., the illustrative systems and devicesof FIGS. 1-4.

FIG. 10 is a flowchart of an illustrative method of detecting atrialactivity using an atrial motion detector for use with, e.g., theillustrative systems and devices of FIGS. 1-4.

FIG. 11 is a flowchart of an illustrative method of detecting heartsounds to represent physiological response information for use with,e.g., the illustrative systems and devices of FIGS. 1-4.

FIG. 12 is a flowchart of an illustrative method of detectingbioimpedance to represent physiological response information for usewith, e.g., the illustrative systems and devices of FIGS. 1-4.

FIG. 13 is a conceptual diagram of an illustrative method for monitoringeffectiveness of left ventricular capture for use with, e.g., theillustrative systems and devices of FIGS. 1-5 and 7-9.

FIG. 14 is a portion of monitored near-field electrogram for use indetermining effectiveness of left ventricular capture for use with,e.g., the illustrative systems and devices of FIGS. 1-5 and 7-9.

FIG. 15 is another conceptual diagram of an illustrative method formonitoring effectiveness of left ventricular capture for use with, e.g.,the illustrative systems and devices of FIGS. 1-5 and 7-9.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The processes, methods, and techniques of this disclosure generallyrelate to implantable medical devices, systems, and methods forventricle-from-atrium (VfA) cardiac resynchronization therapy.Additionally, the processes, methods, and techniques of this disclosuregenerally relate to other cardiac therapy including single chamber ormultiple chamber pacing (e.g., dual or triple chamber pacing),atrioventricular synchronous pacing, asynchronous pacing, triggeredpacing, cardiac resynchronization pacing, or tachycardia-relatedtherapy. Although reference is made herein to implantable medicaldevices, such as a pacemaker or ICD, the methods and processes may beused with any medical devices, systems, or methods related to apatient's heart. Various other applications will become apparent to oneof skill in the art having the benefit of the present disclosure.

It may be beneficial to provide an implantable medical device that isfree of transvenous leads (e.g., a leadless device). It may also bebeneficial to provide an implantable medical device capable of beingused for various cardiac therapies, such as cardiac resynchronizationpacing, single or multiple chamber pacing (e.g., dual or triple chamberpacing), atrioventricular synchronous pacing, asynchronous pacing,triggered pacing, or tachycardia-related therapy. Further, it may bebeneficial to provide a system capable of communicating with a separatemedical device, for example, to provide triggered pacing or to provideshock therapy in certain cases of tachycardia. Further still, it may bebeneficial to configure the implantable medical device to provideadaptive pacing therapy using only an intracardiac device or inconjunction with one or more leads or a separate medical device.

The present disclosure provides an implantable medical device includinga tissue-piercing electrode and optionally a right atrial electrodeand/or a right atrial motion detector. The implantable medical devicemay be a VfA device implanted from the right atrium into the leftventricular myocardium. The implantable medical device may be used inadaptive cardiac therapy, for example, that adapts pacing delays basedon one or more of a measured heartrate, intrinsic AV conduction, etc.Physiological response measurements may be taken, and the VfA device maybe configured to deliver cardiac therapy based on the physiologicalresponse information. In particular, the VfA device may be configured toadapt pacing therapy based on different heartrates and/or intrinsic AVconduction, for example, by determining and delivering pacing therapywith an optimal atrioventricular (AV) pacing delay. Advantageously, inone or more embodiments, the techniques of this disclosure may be usedto calibrate or deliver pacing therapy without using monitoredelectrical activity of the right ventricle of the patient's heart.

The tissue-piercing electrode may be implanted in the basal and/orseptal region of the left ventricular myocardium of the patient's heartfrom the triangle of Koch region of the right atrium through the rightatrial endocardium and central fibrous body. In a leadless implantablemedical device, the tissue-piercing electrode may leadlessly extend froma distal end region of a housing of the device, and the right atrialelectrode may be leadlessly coupled to the housing (e.g., part of orpositioned on the exterior of the housing). In one or more embodiments,a right atrial motion detector may be within the implantable medicaldevice. In a leaded implantable medical device, one or more of theelectrodes may be coupled to the housing using an implantable lead. Whenthe device is implanted, the electrodes may be used to sense electricalactivity in one or more atria and/or ventricles of a patient's heart.The motion detector may be used to sense mechanical activity in one ormore atria and/or ventricles of the patient's heart. In particular, theactivity of the right atrium and the left ventricle may be monitoredand, optionally, the activity of the right ventricle may be monitored.The electrodes may be used to deliver cardiac therapy, such as singlechamber pacing for atrial fibrillation, atrioventricular synchronouspacing for bradycardia, asynchronous pacing, triggered pacing, cardiacresynchronization pacing for ventricular dyssynchrony, anti-tachycardiapacing, or shock therapy. Shock therapy may be initiated by theimplantable medical device. A separate medical device, such as anextravascular ICD, which may also be implanted, may be in operativecommunication with the implantable medical device and may deliver anelectrical shock in response to a trigger, such as a signaling pulse(e.g., triggering, signaling, or distinctive electrical pulse) providedby the device.

FIGS. 1-4 show examples of various cardiac therapy systems that may beconfigured to be used with, for example, the methods shown FIGS. 13-15to monitor left ventricle capture and deliver pacing therapy. Althoughthe present disclosure describes leadless and leaded implantable medicaldevices, reference is first made to FIG. 1 showing a conceptual diagramof a cardiac therapy system 2 including an intracardiac medical device10 that may be configured for single or dual chamber therapy andimplanted in a patient's heart 8. In some embodiments, the device 10 maybe configured for single chamber pacing and may, for example, switchbetween single chamber and multiple chamber pacing (e.g., dual or triplechamber pacing). As used herein, “intracardiac” refers to a deviceconfigured to be implanted entirely within a patient's heart, forexample, to provide cardiac therapy. The device 10 is shown implanted inthe right atrium (RA) of the patient's heart 8 in a target implantregion 4. The device 10 may include one or more fixation members 20 thatanchor a distal end of the device against the atrial endocardium in atarget implant region 4. The target implant region 4 may lie between theBundle of His 5 and the coronary sinus 3 and may be adjacent thetricuspid valve 6. The device 10 may be described as aventricle-from-atrium (VfA) device, which may sense or provide therapyto one or both ventricles (e.g., right ventricle, left ventricle, orboth ventricles, depending on the circumstances) while being generallydisposed in the right atrium. In particular, the device 10 may include atissue-piercing electrode that may be implanted in the basal and/orseptal region of the left ventricular myocardium of the patient's heartfrom the triangle of Koch region of the right atrium through the rightatrial endocardium and central fibrous body.

The device 10 may be described as a leadless implantable medical device.As used herein, “leadless” refers to a device being free of a leadextending out of the patient's heart 8. In other words, a leadlessdevice may have a lead that does not extend from outside of thepatient's heart to inside of the patient's heart. Some leadless devicesmay be introduced through a vein, but once implanted, the device is freeof, or may not include, any transvenous lead and may be configured toprovide cardiac therapy without using any transvenous lead. Further, aleadless VfA device, in particular, does not use a lead to operablyconnect to an electrode in the ventricle when a housing of the device ispositioned in the atrium. Additionally, a leadless electrode may becoupled to the housing of the medical device without using a leadbetween the electrode and the housing.

The device 10 may include a dart electrode assembly 12 defining, orhaving, a straight shaft extending from the distal end region of device10. The dart electrode assembly 12 may be placed, or at least configuredto be placed, through the atrial myocardium and the central fibrous bodyand into the ventricular myocardium 14, or along the ventricular septum,without perforating entirely through the ventricular endocardial orepicardial surfaces. The dart electrode assembly 12 may carry, orinclude, an electrode at the distal end region of the shaft such thatthe electrode may be positioned within the ventricular myocardium forsensing ventricular signals and delivering ventricular pulses (e.g., todepolarize the left ventricle to initiate a contraction of the leftventricle). In some examples, the electrode at the distal end region ofthe shaft is a cathode electrode provided for use in a bipolar electrodepair for pacing and sensing. While the implant region 4 as illustratedmay enable one or more electrodes of the dart electrode assembly 12 tobe positioned in the ventricular myocardium, it is recognized that adevice having the aspects disclosed herein may be implanted at otherlocations for multiple chamber pacing (e.g., dual or triple chamberpacing), single chamber pacing with multiple chamber sensing, singlechamber pacing and/or sensing, or other clinical therapy andapplications as appropriate.

It is to be understood that although device 10 is described herein asincluding a single dart electrode assembly, the device 10 may includemore than one dart electrode assembly placed, or configured to beplaced, through the atrial myocardium and the central fibrous body, andinto the ventricular myocardium 14, or along the ventricular septum,without perforating entirely through the ventricular endocardial orepicardial surfaces. Additionally, each dart electrode assembly maycarry, or include, more than a single electrode at the distal endregion, or along other regions (e.g., proximal or central regions), ofthe shaft.

The cardiac therapy system 2 may also include a separate medical device50 (depicted diagrammatically in FIG. 1), which may be positionedoutside the patient's heart 8 (e.g., subcutaneously) and may be operablycoupled to the patient's heart 8 to deliver cardiac therapy thereto. Inone example, separate medical device 50 may be an extravascular ICD. Insome embodiments, an extravascular ICD may include a defibrillation leadincluding, or carrying, a defibrillation electrode. A therapy vector mayexist between the defibrillation electrode on the defibrillation leadand a housing electrode of the ICD. Further, one or more electrodes ofthe ICD may also be used for sensing electrical signals related to thepatient's heart 8. The ICD may be configured to deliver shock therapyincluding one or more defibrillation or cardioversion shocks. Forexample, if an arrhythmia is sensed, the ICD may send a pulse via theelectrical lead wires to shock the heart and restore its normal rhythm.In some examples, the ICD may deliver shock therapy without placingelectrical lead wires within the heart or attaching electrical wiresdirectly to the heart (subcutaneous ICDs). Examples of extravascular,subcutaneous ICDs that may be used with the system 2 described hereinmay be described in U.S. Pat. No. 9,278,229 (Reinke et al.), issued 8Mar. 2016, which is incorporated herein by reference in its entirety.

In the case of shock therapy (e.g., defibrillation shocks provided bythe defibrillation electrode of the defibrillation lead), the separatemedical device 50 (e.g., extravascular ICD) may include a controlcircuit that uses a therapy delivery circuit to generate defibrillationshocks having any of a number of waveform properties, includingleading-edge voltage, tilt, delivered energy, pulse phases, and thelike. The therapy delivery circuit may, for instance, generatemonophasic, biphasic, or multiphasic waveforms. Additionally, thetherapy delivery circuit may generate defibrillation waveforms havingdifferent amounts of energy. For example, the therapy delivery circuitmay generate defibrillation waveforms that deliver a total of betweenapproximately 60-80 Joules (J) of energy for subcutaneousdefibrillation.

The separate medical device 50 may further include a sensing circuit.The sensing circuit may be configured to obtain electrical signalssensed via one or more combinations of electrodes and to process theobtained signals. The components of the sensing circuit may includeanalog components, digital components, or a combination thereof. Thesensing circuit may, for example, include one or more sense amplifiers,filters, rectifiers, threshold detectors, analog-to-digital converters(ADCs), or the like. The sensing circuit may convert the sensed signalsto digital form and provide the digital signals to the control circuitfor processing and/or analysis. For example, the sensing circuit mayamplify signals from sensing electrodes and convert the amplifiedsignals to multi-bit digital signals by an ADC, and then provide thedigital signals to the control circuit. In one or more embodiments, thesensing circuit may also compare processed signals to a threshold todetect the existence of atrial or ventricular depolarizations (e.g., P-or R-waves) and indicate the existence of the atrial depolarization(e.g., P-waves) or ventricular depolarizations (e.g., R-waves) to thecontrol circuit.

The device 10 and the separate medical device 50 may cooperate toprovide cardiac therapy to the patient's heart 8. For example, thedevice 10 and the separate medical device 50 may be used to detecttachycardia, monitor tachycardia, and/or provide tachycardia-relatedtherapy. For example, the device 10 may communicate with the separatemedical device 50 wirelessly to trigger shock therapy using the separatemedical device 50. As used herein, “wirelessly” refers to an operativecoupling or connection without using a metal conductor between thedevice 10 and the separate medical device 50. In one example, wirelesscommunication may use a distinctive, signaling, or triggeringelectrical-pulse provided by the device 10 that conducts through thepatient's tissue and is detectable by the separate medical device 50. Inanother example, wireless communication may use a communicationinterface (e.g., an antenna) of the device 10 to provide electromagneticradiation that propagates through patient's tissue and is detectable,for example, using a communication interface (e.g., an antenna) of theseparate medical device 50.

With reference to FIG. 2, a leaded medical device 408 includes one, or asingle, implantable lead 410 having a tissue-piercing electrode assembly12 coupled to a distal end region of the lead and implanted inside thepatient's heart 8. The housing 420 of the leaded medical device 408 maybe implanted and positioned outside of the patient's heart 8 and beconfigured to calibrate pacing therapy and/or deliver pacing therapy,for example, based on at least a measured heartrate. The lead 410 mayinclude a right atrial electrode, and the device 408 may operate as adual-channel capable device (e.g., pacing and/or sensing in both theright atrium and left ventricle). In some embodiments, the lead 410 maynot include a right atrial electrode. In other words, the leaded medicaldevice 408 may be a single channel device, which may be used forasynchronous, triggered, or other type of single channel pacing. Theleaded medical device 408, using the lead 410, may sense activity ordeliver pacing to the left ventricle (LV) when the tissue-piercingelectrode assembly 12 is implanted, for example, in the same or similarmanner as described with respect to FIG. 1.

With reference to FIG. 3, leaded medical device 418 is like the leadedmedical device 408 of FIG. 2, except that device 418 includes twoimplantable leads 410, 412. In particular, implantable lead 412 mayinclude an electrode (e.g., a right atrial electrode) coupled to adistal end region of the lead 412 and may be implanted in a differentlocation than lead 410. In some embodiments, lead 412 is implanted in adifferent region of the right atrium. In some embodiments, each lead410, 412 may contribute one channel of a dual-channel device 418. Forexample, lead 410 may sense activity or deliver pacing to the leftventricle (LV) when the tissue-piercing electrode of the tissue-piercingelectrode assembly 12 is implanted, for example, in the same or similarmanner as described with respect to FIG. 1, and lead 412 may senseactivity or deliver pacing to the right atrium (RA).

With reference to FIG. 4, leaded medical device 428 is like leadedmedical device 418 of FIG. 3 except that device 428 includes threeimplantable leads 410, 412, 414. In particular, implantable lead 414 mayinclude an electrode (e.g., a right ventricular electrode) coupled to adistal end region of the lead 414 and may be implanted in a differentlocation than leads 410, 412. In some embodiments, lead 414 is implantedin a region of the right ventricle. In some embodiments, each lead 410,412, 414 may contribute one channel to a multi-channel device 428. Forexample, lead 410 may sense activity or deliver pacing to the leftventricle (LV) when the tissue-piercing electrode assembly 12 isimplanted, for example, in the same or similar manner as described withrespect to FIG. 1, lead 412 may sense activity of deliver pacing to theright atrium (RA), and lead 414 may sense activity or deliver pacing tothe right ventricle (RV).

In some embodiments, a pacing delay between the RV electrode on lead 414to pace the RV and the LV electrode on lead 410 to pace the LV (e.g.,RV-LV pacing delay, or more generally, VV pacing delay) may becalibrated or optimized, for example, using a separate medical device,such as an electrode apparatus (e.g., ECG belt). Various methods may beused to calibrate or optimize the VV delay. In some embodiments, themedical device 428 may be used to test pacing at a plurality ofdifferent VV delays. For example, the RV may be paced ahead of the LV byabout 80, 60, 40, and 20 milliseconds (ms) and the LV may be paced aheadof the RV by about 80, 60, 40, and 20 ms, as well as simultaneous RV-LVpacing (e.g., about 0 ms VV pacing delay). The medical device 428 maythen be configured, for example, automatically, to select a VV pacingdelay that, when used for pacing, corresponds to a minimal electricaldyssynchrony measured using the electrode apparatus. The test pacing atdifferent VV pacing delays may be performed using a particular AV delay,such as a nominal AV delay set by the medical device 428 or at apredetermined optimal AV delay based on patient characteristics.

FIG. 5 is an enlarged conceptual diagram of the intracardiac medicaldevice 10 of FIG. 1 and anatomical structures of the patient's heart 8.In particular, the device 10 is configured to pacing therapy and/ordeliver pacing therapy, for example, based on at least a measuredheartrate. The intracardiac device 10 may include a housing 30. Thehousing 30 may define a hermetically-sealed internal cavity in whichinternal components of the device 10 reside, such as a sensing circuit,therapy delivery circuit, control circuit, memory, telemetry circuit,other optional sensors, and a power source as generally described inconjunction with FIG. 8. The housing 30 may be formed from anelectrically conductive material including titanium or titanium alloy,stainless steel, MP35N (a non-magnetic nickel-cobalt-chromium-molybdenumalloy), platinum alloy, or other bio-compatible metal or metal alloy. Inother examples, the housing 30 may be formed from a non-conductivematerial including ceramic, glass, sapphire, silicone, polyurethane,epoxy, acetyl co-polymer plastics, polyether ether ketone (PEEK), aliquid crystal polymer, or other biocompatible polymer.

In at least one embodiment, the housing 30 may be described as extendingbetween a distal end region 32 and a proximal end region 34 in agenerally cylindrical shape to facilitate catheter delivery. In otherembodiments, the housing 30 may be prismatic or any other shape toperform the functionality and utility described herein. The housing 30may include a delivery tool interface member 26, e.g., at the proximalend region 34, for engaging with a delivery tool during implantation ofthe device 10.

All or a portion of the housing 30 may function as an electrode duringcardiac therapy, for example, in sensing and/or pacing. In the exampleshown, the housing-based electrode 24 is shown to circumscribe aproximal portion (e.g., closer to the proximal end region 34 than thedistal end region 32) of the housing 30. When the housing 30 is formedfrom an electrically conductive material, such as a titanium alloy orother examples listed above, portions of the housing 30 may beelectrically insulated by a non-conductive material, such as a coatingof parylene, polyurethane, silicone, epoxy, or other biocompatiblepolymer, leaving one or more discrete areas of conductive materialexposed to define the proximal housing-based electrode 24. When thehousing 30 is formed from a non-conductive material, such as a ceramic,glass or polymer material, an electrically-conductive coating or layer,such as a titanium, platinum, stainless steel, or alloys thereof, may beapplied to one or more discrete areas of the housing 30 to form theproximal housing-based electrode 24. In other examples, the proximalhousing-based electrode 24 may be a component, such as a ring electrode,that is mounted or assembled onto the housing 30. The proximalhousing-based electrode 24 may be electrically coupled to internalcircuitry of the device 10, e.g., via the electrically-conductivehousing 30 or an electrical conductor when the housing 30 is anon-conductive material.

In the example shown, the proximal housing-based electrode 24 is locatednearer to the housing proximal end region 34 than the housing distal endregion 32 and is therefore referred to as a “proximal housing-basedelectrode” 24. In other examples, however, the housing-based electrode24 may be located at other positions along the housing 30, e.g., moredistal relative to the position shown.

At the distal end region 32, the device 10 may include a distal fixationand electrode assembly 36, which may include one or more fixationmembers 20 and one or more dart electrode assemblies 12 of equal orunequal length. In one example, a single dart electrode assembly 12includes a shaft 40 extending distally away from the housing distal endregion 32 and one or more electrode elements, such as a tip electrode 42at or near the free, distal end region of the shaft 40. The tipelectrode 42 may have a conical or hemi-spherical distal tip with arelatively narrow tip-diameter (e.g., less than about 1 millimeter (mm))for penetrating into and through tissue layers without using a sharpenedtip or needle-like tip having sharpened or beveled edges.

The shaft 40 of the dart electrode assembly 12 may be a normallystraight member and may be rigid. In other embodiments, the shaft 40 maybe described as being relatively stiff but still possessing limitedflexibility in lateral directions. Further, the shaft 40 may benon-rigid to allow some lateral flexing with heart motion. However, in arelaxed state, when not subjected to any external forces, the shaft 40may maintain a straight position as shown to hold the tip electrode 42spaced apart from the housing distal end region 32 at least by theheight 47 of the shaft 40. In other words, the dart electrode assembly12 may be described as resilient.

The dart electrode assembly 12 may be configured to pierce through oneor more tissue layers to position the tip electrode 42 within a desiredtissue layer, e.g., the ventricular myocardium. As such, the height 47,or length, of the shaft 40 may correspond to the expected pacing sitedepth, and the shaft 40 may have a relatively high compressive strengthalong its longitudinal axis to resist bending in a lateral or radialdirection when pressed against the implant region 4. If a second dartelectrode assembly 12 is employed, its length may be unequal to theexpected pacing site depth and may be configured to act as anindifferent electrode for delivering of pacing energy to the tissue. Alongitudinal axial force may be applied against the tip electrode 42,e.g., by applying longitudinal pushing force to the proximal end 34 ofthe housing 30, to advance the dart electrode assembly 12 into thetissue within the target implant region. The shaft 40 may be describedas longitudinally non-compressive and/or elastically deformable inlateral or radial directions when subjected to lateral or radial forcesto allow temporary flexing, e.g., with tissue motion, but may return toits normally straight position when lateral forces diminish. When theshaft 40 is not exposed to any external force, or to only a force alongits longitudinal central axis, the shaft 40 may retain a straight,linear position as shown.

The one or more fixation members 20 may be described as one or more“tines” having a normally curved position. The tines may be held in adistally extended position within a delivery tool. The distal tips oftines may penetrate the heart tissue to a limited depth beforeelastically curving back proximally into the normally curved position(shown) upon release from the delivery tool. Further, the fixationmembers 20 may include one or more aspects described in, for example,U.S. Pat. No. 9,675,579 (Grubac et al.), issued 13 Jun. 2017, and U.S.Pat. No. 9,119,959 (Rys et al.), issued 1 Sep. 2015, each of which isincorporated herein by reference in its entirety.

In some examples, the distal fixation and electrode assembly 36 includesa distal housing-based electrode 22. In the case of using the device 10as a pacemaker for multiple chamber pacing (e.g., dual or triple chamberpacing) and sensing, the tip electrode 42 may be used as a cathodeelectrode paired with the proximal housing-based electrode 24 serving asa return anode electrode. Alternatively, the distal housing-basedelectrode 22 may serve as a return anode electrode paired with tipelectrode 42 for sensing ventricular signals and delivering ventricularpacing pulses. In other examples, the distal housing-based electrode 22may be a cathode electrode for sensing atrial signals and deliveringpacing pulses to the atrial myocardium in the target implant region 4.When the distal housing-based electrode 22 serves as an atrial cathodeelectrode, the proximal housing-based electrode 24 may serve as thereturn anode paired with the tip electrode 42 for ventricular pacing andsensing and as the return anode paired with the distal housing-basedelectrode 22 for atrial pacing and sensing.

As shown in this illustration, the target implant region 4 in somepacing applications is along the atrial endocardium 18, generallyinferior to the AV node 15 and the His bundle 5. The dart electrodeassembly 12 may at least partially define the height 47, or length, ofthe shaft 40 for penetrating through the atrial endocardium 18 in thetarget implant region 4, through the central fibrous body 16, and intothe ventricular myocardium 14 without perforating through theventricular endocardial surface 17. When the height 47, or length, ofthe dart electrode assembly 12 is fully advanced into the target implantregion 4, the tip electrode 42 may rest within the ventricularmyocardium 14, and the distal housing-based electrode 22 may bepositioned in intimate contact with or close proximity to the atrialendocardium 18. The dart electrode assembly 12 may have a total combinedheight 47, or length, of tip electrode 42 and shaft 40 from about 3 mmto about 8 mm in various examples. The diameter of the shaft 40 may beless than about 2 mm, and may be about 1 mm or less, or even about 0.6mm or less.

The device 10 may include an acoustic or motion detector 11 within thehousing 30. The acoustic or motion detector 11 may be operably coupledto one or more a control circuit 80 (FIG. 8), a sensing circuit 86 (FIG.8), or therapy delivery circuit 84 (FIG. 8). In some embodiments, theacoustic or motion detector 11 may be used with methods 600, 650, or 800as shown in FIGS. 10-12. The acoustic or motion detector 11 may be usedto monitor mechanical activity, such as atrial mechanical activity(e.g., an atrial contraction) and/or ventricular mechanical activity(e.g., a ventricular contraction). In some embodiments, the acoustic ormotion detector 11 may be used to detect right atrial mechanicalactivity. A non-limiting example of an acoustic or motion detector 11includes an accelerometer or microphone. In some embodiments, themechanical activity detected by the acoustic or motion detector 11 maybe used to supplement or replace electrical activity detected by one ormore of the electrodes of the device 10. For example, the acoustic ormotion detector 11 may be used in addition to, or as an alternative to,the proximal housing-based electrode 24.

The acoustic or motion detector 11 may also be used for rate responsedetection or to provide a rate-responsive IMD. Various techniquesrelated to rate response may be described in U.S. Pat. No. 5,154,170(Bennett et al.), issued Oct. 13, 1992, entitled “Optimization for rateresponsive cardiac pacemaker,” and U.S. Pat. No. 5,562,711 (Yerich etal.), issued Oct. 8, 1996, entitled “Method and apparatus forrate-responsive cardiac pacing,” each of which is incorporated herein byreference in its entirety.

In various embodiments, acoustic or motion sensor 11 may be used as anHS sensor and may be implemented as a microphone or a 1-, 2- or 3-axisaccelerometer. In one embodiment, the acoustical sensor is implementedas a piezoelectric crystal mounted within an implantable medical devicehousing and responsive to the mechanical motion associated with heartsounds. The piezoelectric crystal may be a dedicated HS sensor or may beused for multiple functions. In the illustrative embodiment shown, theacoustical sensor is embodied as a piezoelectric crystal that is alsoused to generate a patient alert signal in the form of a perceptiblevibration of the IMD housing. Upon detecting an alert condition, controlcircuit 80 may cause patient alert control circuitry to generate analert signal by activating the piezoelectric crystal.

Control circuit may be used to control whether the piezoelectric crystalis used in a “listening mode” to sense HS signals by HS sensingcircuitry or in an “output mode” to generate a patient alert. Duringpatient alert generation, HS sensing circuitry may be temporarilydecoupled from the HS sensor by control circuitry.

Examples of other embodiments of acoustical sensors that may be adaptedfor implementation with the techniques of the present disclosure may bedescribed generally in U.S. Pat. No. 4,546,777 (Groch, et al.), U.S.Pat. No. 6,869,404 (Schulhauser, et al.), U.S. Pat. No. 5,554,177(Kieval, et al.), and U.S. Pat. No. 7,035,684 (Lee, et al.), each ofwhich is incorporated herein by reference in its entirety.

Various types of acoustical sensors may be used. The acoustical sensormay be any implantable or external sensor responsive to one or more ofthe heart sounds generated as described in the foregoing and therebyproduces an electrical analog signal correlated in time and amplitude tothe heart sounds. The analog signal may be then be processed, which mayinclude digital conversion, by the HS sensing module to obtain HSparameters, such as amplitudes or relative time intervals, as derived byHS sensing module or control circuit 80. The acoustical sensor and HSsensing module may be incorporated in an IMD capable of delivering CRTor another cardiac therapy being optimized or may be implemented in aseparate device having wired or wireless communication with IMD or anexternal programmer or computer used during a pace parameteroptimization procedure as described herein.

FIG. 6 is a two-dimensional (2D) ventricular map 300 of a patient'sheart (e.g., a top-down view) showing the left ventricle 320 in astandard 17 segment view and the right ventricle 322. The map 300includes a plurality of areas 326 corresponding to different regions ofa human heart. As illustrated, the areas 326 are numerically labeled1-17 (which, e.g., correspond to a standard 17 segment model of a humanheart, correspond to 17 segments of the left ventricle of a human heart,etc.). Areas 326 of the map 300 may include basal anterior area 1, basalanteroseptal area 2, basal inferoseptal area 3, basal inferior area 4,basal inferolateral area 5, basal anterolateral area 6, mid-anteriorarea 7, mid-anteroseptal area 8, mid-inferoseptal area 9, mid-inferiorarea 10, mid-inferolateral area 11, mid-anterolateral area 12, apicalanterior area 13, apical septal area 14, apical inferior area 15, apicallateral area 16, and apex area 17. The inferoseptal and anteroseptalareas of the right ventricle 322 are also illustrated, as well as theright bunch branch (RBB) and left bundle branch (LBB).

In some embodiments, any of the tissue-piercing electrodes of thepresent disclosure may be implanted in the basal and/or septal region ofthe left ventricular myocardium of the patient's heart. In particular,the tissue-piercing electrode may be implanted from the triangle of Kochregion of the right atrium through the right atrial endocardium andcentral fibrous body.

Once implanted, the tissue-piercing electrode may be positioned in thetarget implant region 4 (FIGS. 1-5), such as the basal and/or septalregion of the left ventricular myocardium. With reference to map 300,the basal region includes one or more of the basal anterior area 1,basal anteroseptal area 2, basal inferoseptal area 3, basal inferiorarea 4, mid-anterior area 7, mid-anteroseptal area 8, mid-inferoseptalarea 9, and mid-inferior area 10. With reference to map 300, the septalregion includes one or more of the basal anteroseptal area 2, basalanteroseptal area 3, mid-anteroseptal area 8, mid-inferoseptal area 9,and apical septal area 14.

In some embodiments, the tissue-piercing electrode may be positioned inthe basal septal region of the left ventricular myocardium whenimplanted. The basal septal region may include one or more of the basalanteroseptal area 2, basal inferoseptal area 3, mid-anteroseptal area 8,and mid-inferoseptal area 9.

In some embodiments, the tissue-piercing electrode may be positioned inthe high inferior/posterior basal septal region of the left ventricularmyocardium when implanted. The high inferior/posterior basal septalregion of the left ventricular myocardium may include a portion of oneor more of the basal inferoseptal area 3 and mid-inferoseptal area 9(e.g., the basal inferoseptal area only, the mid-inferoseptal area only,or both the basal inferoseptal area and the mid-inferoseptal area). Forexample, the high inferior/posterior basal septal region may includeregion 324 illustrated generally as a dashed-line boundary. As shown,the dashed line boundary represents an approximation of where the highinferior/posterior basal septal region is located, which may take asomewhat different shape or size depending on the particularapplication.

FIG. 7 is a three-dimensional perspective view of the device 10 capableof calibrating pacing therapy and/or delivering pacing therapy, forexample, based on at least a measured heartrate. As shown, the distalfixation and electrode assembly 36 includes the distal housing-basedelectrode 22 implemented as a ring electrode. The distal housing-basedelectrode 22 may be positioned in intimate contact with or operativeproximity to atrial tissue when fixation member tines 20 a, 20 b and 20c of the fixation members 20, engage with the atrial tissue. The tines20 a, 20 b and 20 c, which may be elastically deformable, may beextended distally during delivery of device 10 to the implant site. Forexample, the tines 20 a, 20 b, and 20 c may pierce the atrialendocardial surface as the device 10 is advanced out of the deliverytool and flex back into their normally curved position (as shown) whenno longer constrained within the delivery tool. As the tines 20 a, 20 band 20 c curve back into their normal position, the fixation member 20may pull the distal fixation member and electrode assembly 36 toward theatrial endocardial surface. As the distal fixation member and electrodeassembly 36 is pulled toward the atrial endocardium, the tip electrode42 may be advanced through the atrial myocardium and the central fibrousbody and into the ventricular myocardium. The distal housing-basedelectrode 22 may then be positioned against the atrial endocardialsurface.

The distal housing-based electrode 22 may include a ring formed of anelectrically conductive material, such as titanium, platinum, iridium,or alloys thereof. The distal housing-based electrode 22 may be asingle, continuous ring electrode. In other examples, portions of thering may be coated with an electrically insulating coating, e.g.,parylene, polyurethane, silicone, epoxy, or other insulating coating, toreduce the electrically conductive surface area of the ring electrode.For instance, one or more sectors of the ring may be coated to separatetwo or more electrically conductive exposed surface areas of the distalhousing-based electrode 22. Reducing the electrically conductive surfacearea of the distal housing-based electrode 22, e.g., by coveringportions of the electrically conductive ring with an insulating coating,may increase the electrical impedance of the distal housing-based 22,and thereby, reduce the current delivered during a pacing pulse thatcaptures the myocardium, e.g., the atrial myocardial tissue. A lowercurrent drain may conserve the power source, e.g., one or morerechargeable or non-rechargeable batteries, of the device 10.

As described above, the distal housing-based electrode 22 may beconfigured as an atrial cathode electrode for delivering pacing pulsesto the atrial tissue at the implant site in combination with theproximal housing-based electrode 24 as the return anode. The electrodes22 and 24 may be used to sense atrial P-waves for use in controllingatrial pacing pulses (delivered in the absence of a sensed P-wave) andfor controlling atrial-synchronized ventricular pacing pulses deliveredusing the tip electrode 42 as a cathode and the proximal housing-basedelectrode 24 as the return anode. In other examples, the distalhousing-based electrode 22 may be used as a return anode in conjunctionwith the cathode tip electrode 42 for ventricular pacing and sensing.

FIG. 8 is a block diagram of circuitry that may be enclosed within thehousing 30 (FIG. 7) to provide the functions of calibrating pacingtherapy and/or delivering pacing therapy, for example, based on at leasta measured heartrate, using the device 10 according to one example orwithin the housings of any other medical devices described herein (e.g.,device 408 of FIG. 2, device 418 of FIG. 3, device 428 of FIG. 4, ordevice 710 of FIG. 9). The separate medical device 50 (FIGS. 1-4) mayinclude some or all the same components, which may be configured in asimilar manner. The electronic circuitry enclosed within housing 30 mayinclude software, firmware, and hardware that cooperatively monitoratrial and ventricular electrical cardiac signals, determine when acardiac therapy is necessary, and/or deliver electrical pulses to thepatient's heart according to programmed therapy mode and pulse controlparameters. The electronic circuitry may include a control circuit 80(e.g., including processing circuitry), a memory 82, a therapy deliverycircuit 84, a sensing circuit 86, and/or a telemetry circuit 88. In someexamples, the device 10 includes one or more sensors 90 for producing asignal that is correlated to a physiological function, state, orcondition of the patient, such as a patient activity sensor, for use indetermining a need for pacing therapy and/or controlling a pacing rate.For example, one sensor 90 may include an inertial measurement unit(e.g., accelerometer) to measure motion.

The power source 98 may provide power to the circuitry of the device 10including each of the components 80, 82, 84, 86, 88, 90 as needed. Thepower source 98 may include one or more energy storage devices, such asone or more rechargeable or non-rechargeable batteries. The connections(not shown) between the power source 98 and each of the components 80,82, 84, 86, 88, 90 may be understood from the general block diagramillustrated to one of ordinary skill in the art. For example, the powersource 98 may be coupled to one or more charging circuits included inthe therapy delivery circuit 84 for providing the power used to chargeholding capacitors included in the therapy delivery circuit 84 that aredischarged at appropriate times under the control of the control circuit80 for delivering pacing pulses, e.g., according to a dual chamberpacing mode such as DDI(R). The power source 98 may also be coupled tocomponents of the sensing circuit 86, such as sense amplifiers,analog-to-digital converters, switching circuitry, etc., sensors 90, thetelemetry circuit 88, and the memory 82 to provide power to the variouscircuits.

The functional blocks shown represent functionality included in thedevice 10 and may include any discrete and/or integrated electroniccircuit components that implement analog, and/or digital circuitscapable of producing the functions attributed to the medical device 10herein. The various components may include processing circuitry, such asan application specific integrated circuit (ASIC), an electroniccircuit, a processor (shared, dedicated, or group), and memory thatexecute one or more software or firmware programs, a combinational logiccircuit, state machine, or other suitable components or combinations ofcomponents that provide the described functionality. The particular formof software, hardware, and/or firmware employed to implement thefunctionality disclosed herein will be determined primarily by theparticular system architecture employed in the medical device and by theparticular detection and therapy delivery methodologies employed by themedical device.

The memory 82 may include any volatile, non-volatile, magnetic, orelectrical non-transitory computer readable storage media, such asrandom-access memory (RAM), read-only memory (ROM), non-volatile RAM(NVRAM), electrically-erasable programmable ROM (EEPROM), flash memory,or any other memory device. Furthermore, the memory 82 may include anon-transitory computer readable media storing instructions that, whenexecuted by one or more processing circuits, cause the control circuit80 and/or other processing circuitry to calibrate pacing therapy and/orperform a single, dual, or triple chamber calibrated pacing therapy(e.g., single or multiple chamber pacing), or other cardiac therapyfunctions (e.g., sensing or delivering therapy), attributed to thedevice 10. The non-transitory computer-readable media storing theinstructions may include any of the media listed above.

The control circuit 80 may communicate, e.g., via a data bus, with thetherapy delivery circuit 84 and the sensing circuit 86 for sensingcardiac electrical signals and controlling delivery of cardiacelectrical stimulation therapies in response to sensed cardiac events,e.g., P-waves and R-waves, or the absence thereof. The tip electrode 42,the distal housing-based electrode 22, and the proximal housing-basedelectrode 24 may be electrically coupled to the therapy delivery circuit84 for delivering electrical stimulation pulses to the patient's heartand to the sensing circuit 86 and for sensing cardiac electricalsignals.

The sensing circuit 86 may include an atrial (A) sensing channel 87 anda ventricular (V) sensing channel 89. The distal housing-based electrode22 and the proximal housing-based electrode 24 may be coupled to theatrial sensing channel 87 for sensing atrial signals, e.g., P-wavesattendant to the depolarization of the atrial myocardium. In examplesthat include two or more selectable distal housing-based electrodes, thesensing circuit 86 may include switching circuitry for selectivelycoupling one or more of the available distal housing-based electrodes tocardiac event detection circuitry included in the atrial sensing channel87. Switching circuitry may include a switch array, switch matrix,multiplexer, or any other type of switching device suitable toselectively couple components of the sensing circuit 86 to selectedelectrodes. The tip electrode 42 and the proximal housing-basedelectrode 24 may be coupled to the ventricular sensing channel 89 forsensing ventricular signals, e.g., R-waves attendant to thedepolarization of the ventricular myocardium.

Each of the atrial sensing channel 87 and the ventricular sensingchannel 89 may include cardiac event detection circuitry for detectingP-waves and R-waves, respectively, from the cardiac electrical signalsreceived by the respective sensing channels. The cardiac event detectioncircuitry included in each of the channels 87 and 89 may be configuredto amplify, filter, digitize, and rectify the cardiac electrical signalreceived from the selected electrodes to improve the signal quality fordetecting cardiac electrical events. The cardiac event detectioncircuitry within each channel 87 and 89 may include one or more senseamplifiers, filters, rectifiers, threshold detectors, comparators,analog-to-digital converters (ADCs), timers, or other analog or digitalcomponents. A cardiac event sensing threshold, e.g., a P-wave sensingthreshold and an R-wave sensing threshold, may be automatically adjustedby each respective sensing channel 87 and 89 under the control of thecontrol circuit 80, e.g., based on timing intervals and sensingthreshold values determined by the control circuit 80, stored in thememory 82, and/or controlled by hardware, firmware, and/or software ofthe control circuit 80 and/or the sensing circuit 86.

Upon detecting a cardiac electrical event based on a sensing thresholdcrossing, the sensing circuit 86 may produce a sensed event signal thatis passed to the control circuit 80. For example, the atrial sensingchannel 87 may produce a P-wave sensed event signal in response to aP-wave sensing threshold crossing. The ventricular sensing channel 89may produce an R-wave sensed event signal in response to an R-wavesensing threshold crossing. The sensed event signals may be used by thecontrol circuit 80 for setting pacing escape interval timers thatcontrol the basic time intervals used for scheduling cardiac pacingpulses. A sensed event signal may trigger or inhibit a pacing pulsedepending on the particular programmed pacing mode. For example, aP-wave sensed event signal received from the atrial sensing channel 87may cause the control circuit 80 to inhibit a scheduled atrial pacingpulse and schedule a ventricular pacing pulse at a programmedatrioventricular (AV) pacing interval. If an R-wave is sensed before theAV pacing interval expires, the ventricular pacing pulse may beinhibited. If the AV pacing interval expires before the control circuit80 receives an R-wave sensed event signal from the ventricular sensingchannel 89, the control circuit 80 may use the therapy delivery circuit84 to deliver the scheduled ventricular pacing pulse synchronized to thesensed P-wave.

In some examples, the device 10 may be configured to deliver a varietyof pacing therapies including bradycardia pacing, cardiacresynchronization therapy, post-shock pacing, and/or tachycardia-relatedtherapy, such as ATP, among others. For example, the device 10 may beconfigured to detect non-sinus tachycardia and deliver ATP. The controlcircuit 80 may determine cardiac event time intervals, e.g., P-Pintervals between consecutive P-wave sensed event signals received fromthe atrial sensing channel 87, R-R intervals between consecutive R-wavesensed event signals received from the ventricular sensing channel 89,and P-R and/or R-P intervals received between P-wave sensed eventsignals and R-wave sensed event signals. These intervals may be comparedto tachycardia detection intervals for detecting non-sinus tachycardia.Tachycardia may be detected in a given heart chamber based on athreshold number of tachycardia detection intervals being detected.

The therapy delivery circuit 84 may include atrial pacing circuit 83 andventricular pacing circuit 85. Each pacing circuit 83, 85 may includecharging circuitry, one or more charge storage devices such as one ormore low voltage holding capacitors, an output capacitor, and/orswitching circuitry that controls when the holding capacitor(s) arecharged and discharged across the output capacitor to deliver a pacingpulse to the pacing electrode vector coupled to respective pacingcircuits 83, 85. The tip electrode 42 and the proximal housing-basedelectrode 24 may be coupled to the ventricular pacing circuit 85 as abipolar cathode and anode pair for delivering ventricular pacing pulses,e.g., upon expiration of an AV or VV pacing interval set by the controlcircuit 80 for providing atrial-synchronized ventricular pacing and abasic lower ventricular pacing rate.

The atrial pacing circuit 83 may be coupled to the distal housing-basedelectrode 22 and the proximal housing-based electrode 24 to deliveratrial pacing pulses. The control circuit 80 may set one or more atrialpacing intervals according to a programmed lower pacing rate or atemporary lower rate set according to a rate-responsive sensor indicatedpacing rate. Atrial pacing circuit may be controlled to deliver anatrial pacing pulse if the atrial pacing interval expires before aP-wave sensed event signal is received from the atrial sensing channel87. The control circuit 80 starts an AV pacing interval in response to adelivered atrial pacing pulse to provide synchronized multiple chamberpacing (e.g., dual or triple chamber pacing).

Charging of a holding capacitor of the atrial or ventricular pacingcircuit 83, 85 to a programmed pacing voltage amplitude and dischargingof the capacitor for a programmed pacing pulse width may be performed bythe therapy delivery circuit 84 according to control signals receivedfrom the control circuit 80. For example, a pace timing circuit includedin the control circuit 80 may include programmable digital counters setby a microprocessor of the control circuit 80 for controlling the basicpacing time intervals associated with various single chamber or multiplechamber pacing (e.g., dual or triple chamber pacing) modes oranti-tachycardia pacing sequences. The microprocessor of the controlcircuit 80 may also set the amplitude, pulse width, polarity, or othercharacteristics of the cardiac pacing pulses, which may be based onprogrammed values stored in the memory 82.

The device 10 may include other sensors 90 for sensing signals from thepatient for use in determining a need for and/or controlling electricalstimulation therapies delivered by the therapy delivery circuit 84. Insome examples, a sensor indicative of a need for increased cardiacoutput may include a patient activity sensor, such as an accelerometer.An increase in the metabolic demand of the patient due to increasedactivity as indicated by the patient activity sensor may be determinedby the control circuit 80 for use in determining a sensor-indicatedpacing rate. The control circuit 80 may be used to calibrate and/ordeliver pacing therapy based on the patient activity sensor (e.g., ameasured heartrate).

Control parameters utilized by the control circuit 80 for sensingcardiac events and controlling pacing therapy delivery may be programmedinto the memory 82 via the telemetry circuit 88, which may also bedescribed as a communication interface. The telemetry circuit 88includes a transceiver and antenna for communicating with an externaldevice, such as a programmer or home monitor, using radio frequencycommunication or other communication protocols. The control circuit 80may use the telemetry circuit 88 to receive downlink telemetry from andsend uplink telemetry to the external device. In some cases, thetelemetry circuit 88 may be used to transmit and receive communicationsignals to/from another medical device implanted in the patient.

FIG. 9 is a three-dimensional perspective view of another leadlessintracardiac medical device 710 that may be configured for calibratingpacing therapy and/or delivering pacing therapy, for example, based onat least a measured heartrate, for single or multiple chamber cardiactherapy (e.g., dual or triple chamber cardiac therapy) according toanother example. The device 710 may include a housing 730 having anouter sidewall 735, shown as a cylindrical outer sidewall, extendingfrom a housing distal end region 732 to a housing proximal end region734. The housing 730 may enclose electronic circuitry configured toperform single or multiple chamber cardiac therapy, including atrial andventricular cardiac electrical signal sensing and pacing the atrial andventricular chambers. Delivery tool interface member 726 is shown on thehousing proximal end region 734.

A distal fixation and electrode assembly 736 may be coupled to thehousing distal end region 732. The distal fixation and electrodeassembly 736 may include an electrically insulative distal member 772coupled to the housing distal end region 732. The tissue-piercingelectrode assembly 712 extends away from the housing distal end region732, and multiple non-tissue piercing electrodes 722 may be coupleddirectly to the insulative distal member 772. The tissue-piercingelectrode assembly 712 extends in a longitudinal direction away from thehousing distal end region 732 and may be coaxial with the longitudinalcenter axis 731 of the housing 730.

The distal tissue-piercing electrode assembly 712 may include anelectrically insulated shaft 740 and a tip electrode 742 (e.g.,tissue-piercing electrode). In some examples, the tissue-piercingelectrode assembly 712 is an active fixation member including a helicalshaft 740 and a distal cathode tip electrode 742. The helical shaft 740may extend from a shaft distal end region 743 to a shaft proximal endregion 741, which may be directly coupled to the insulative distalmember 772. The helical shaft 740 may be coated with an electricallyinsulating material, e.g., parylene or other examples listed herein, toavoid sensing or stimulation of cardiac tissue along the shaft length.The tip electrode 742 is at the shaft distal end region 743 and mayserve as a cathode electrode for delivering ventricular pacing pulsesand sensing ventricular electrical signals using the proximalhousing-based electrode 724 as a return anode when the tip electrode 742is advanced into ventricular tissue. The proximal housing-basedelectrode 724 may be a ring electrode circumscribing the housing 730 andmay be defined by an uninsulated portion of the longitudinal sidewall735. Other portions of the housing 730 not serving as an electrode maybe coated with an electrically insulating material as described above inconjunction with FIG. 7.

Using two or more tissue-piercing electrodes (e.g., of any type)penetrating into the LV myocardium may be used for more localized pacingcapture and may mitigate ventricular pacing spikes affecting capturingatrial tissue. In some embodiments, multiple tissue-piercing electrodesmay include two or more dart-type electrode assemblies (e.g., electrodeassembly 12 of FIG. 7), a helical-type electrode (e.g., electrodeassembly 712) Non-limiting examples of multiple tissue-piercingelectrodes include two dart electrode assemblies, a helix electrode witha dart electrode assembly extending therethrough (e.g., through thecenter), or dual intertwined helixes. Multiple tissue-piercingelectrodes may also be used for bipolar or multi-polar pacing.

In some embodiments, one or more tissue-piercing electrodes (e.g., ofany type) that penetrate into the LV myocardium may be a multi-polartissue-piercing electrode. A multi-polar tissue-piercing electrode mayinclude one or more electrically active and electrically separateelements, which may enable bipolar or multi-polar pacing from one ormore tissue-piercing electrodes.

Multiple non-tissue piercing electrodes 722 may be provided along aperiphery of the insulative distal member 772, peripheral to thetissue-piercing electrode assembly 712. The insulative distal member 772may define a distal-facing surface 738 of the device 710 and acircumferential surface 739 that circumscribes the device 710 adjacentto the housing longitudinal sidewall 735. Non-tissue piercing electrodes722 may be formed of an electrically conductive material, such astitanium, platinum, iridium, or alloys thereof. In the illustratedembodiment, six non-tissue piercing electrodes 722 are spaced apartradially at equal distances along the outer periphery of insulativedistal member 772, however, two or more non-tissue piercing electrodes722 may be provided.

Non-tissue piercing electrodes 722 may be discrete components eachretained within a respective recess 774 in the insulative member 772sized and shaped to mate with the non-tissue piercing electrode 722. Inother examples, the non-tissue piercing electrodes 722 may each be anuninsulated, exposed portion of a unitary member mounted within or onthe insulative distal member 772. Intervening portions of the unitarymember not functioning as an electrode may be insulated by theinsulative distal member 772 or, if exposed to the surroundingenvironment, may be coated with an electrically insulating coating,e.g., parylene, polyurethane, silicone, epoxy, or other insulatingcoating.

When the tissue-piercing electrode assembly 712 is advanced into cardiactissue, at least one non-tissue piercing electrode 722 may be positionedagainst, in intimate contact with, or in operative proximity to, acardiac tissue surface for delivering pulses and/or sensing cardiacelectrical signals produced by the patient's heart. For example,non-tissue piercing electrodes 722 may be positioned in contact withright atrial endocardial tissue for pacing and sensing in the atriumwhen the tissue-piercing electrode assembly 712 is advanced into theatrial tissue and through the central fibrous body until the distal tipelectrode 742 is positioned in direct contact with ventricular tissue,e.g., ventricular myocardium and/or a portion of the ventricularconduction system.

Non-tissue piercing electrodes 722 may be coupled to the therapydelivery circuit 84 and the sensing circuit 86 (see FIG. 8) enclosed bythe housing 730 to function collectively as a cathode electrode fordelivering atrial pacing pulses and for sensing atrial electricalsignals, e.g., P-waves, in combination with the proximal housing-basedelectrode 724 as a return anode. Switching circuitry included in thesensing circuit 86 may be activated under the control of the controlcircuit 80 to couple one or more of the non-tissue piercing electrodesto the atrial sensing channel 87. Distal, non-tissue piercing electrodes722 may be electrically isolated from each other so that each individualone of the electrodes 722 may be individually selected by switchingcircuitry included in the therapy delivery circuit 84 to serve alone orin a combination of two or more of the electrodes 722 as an atrialcathode electrode. Switching circuitry included in the therapy deliverycircuit 84 may be activated under the control of the control circuit 80to couple one or more of the non-tissue piercing electrodes 722 to theatrial pacing circuit 83. Two or more of the non-tissue piercingelectrodes 722 may be selected at a time to operate as a multi-pointatrial cathode electrode.

Certain non-tissue piercing electrodes 722 selected for atrial pacingand/or atrial sensing may be selected based on atrial capture thresholdtests, electrode impedance, P-wave signal strength in the cardiacelectrical signal, or other factors. For example, a single one or anycombination of two or more individual non-tissue piercing electrodes 722functioning as a cathode electrode that provides an optimal combinationof a low pacing capture threshold amplitude and relatively highelectrode impedance may be selected to achieve reliable atrial pacingusing minimal current drain from the power source 98.

In some instances, the distal-facing surface 738 may uniformly contactthe atrial endocardial surface when the tissue-piercing electrodeassembly 712 anchors the housing 730 at the implant site. In that case,all the electrodes 722 may be selected together to form the atrialcathode. Alternatively, every other one of the electrodes 722 may beselected together to form a multi-point atrial cathode having a higherelectrical impedance that is still uniformly distributed along thedistal-facing surface 738. Alternatively, a subset of one or moreelectrodes 722 along one side of the insulative distal member 772 may beselected to provide pacing at a desired site that achieves the lowestpacing capture threshold due to the relative location of the electrodes722 to the atrial tissue being paced.

In other instances, the distal-facing surface 738 may be oriented at anangle relative to the adjacent endocardial surface depending on thepositioning and orientation at which the tissue-piercing electrodeassembly 712 enters the cardiac tissue. In this situation, one or moreof the non-tissue piercing electrodes 722 may be positioned in closercontact with the adjacent endocardial tissue than other non-tissuepiercing electrodes 722, which may be angled away from the endocardialsurface. By providing multiple non-tissue piercing electrodes along theperiphery of the insulative distal member 772, the angle of thetissue-piercing electrode assembly 712 and the housing distal end region732 relative to the cardiac surface, e.g., the right atrial endocardialsurface, may not be required to be substantially parallel. Anatomicaland positional differences may cause the distal-facing surface 738 to beangled or oblique to the endocardial surface, however, multiplenon-tissue piercing electrodes 722 distributed along the periphery ofthe insulative distal member 772 increase the likelihood of good contactbetween one or more electrodes 722 and the adjacent cardiac tissue topromote acceptable pacing thresholds and reliable cardiac event sensingusing at least a subset of multiple electrodes 722. Contact or fixationcircumferentially along the entire periphery of the insulative distalmember 772 may not be required.

The non-tissue piercing electrodes 722 are shown to each include a firstportion 722 a extending along the distal-facing surface 738 and a secondportion 722 b extending along the circumferential surface 739. The firstportion 722 a and the second portion 722 b may be continuous exposedsurfaces such that the active electrode surface wraps around aperipheral edge 776 of the insulative distal member 772 that joins thedistal facing surface 738 and the circumferential surface 739. Thenon-tissue piercing electrodes 722 may include one or more of theelectrodes 722 along the distal-facing surface 738, one or moreelectrodes along the circumferential surface 739, one or more electrodeseach extending along both of the distal-facing surface 738 and thecircumferential surface 739, or any combination thereof. The exposedsurface of each of the non-tissue piercing electrodes 722 may be flushwith respective distal-facing surfaces 738 and/or circumferentialsurfaces. In other examples, each of the non-tissue piercing electrodes722 may have a raised surface that protrudes from the insulative distalmember 772. Any raised surface of the electrodes 722, however, maydefine a smooth or rounded, non-tissue piercing surface.

The distal fixation and electrode assembly 736 may seal the distal endregion of the housing 730 and may provide a foundation on which theelectrodes 722 are mounted. The electrodes 722 may be referred to ashousing-based electrodes. The electrodes 722 may not be not carried by ashaft or other extension that extends the active electrode portion awayfrom the housing 730, like the distal tip electrode 742 residing at thedistal tip of the helical shaft 740 extending away from the housing 730.Other examples of non-tissue piercing electrodes presented herein thatare coupled to a distal-facing surface and/or a circumferential surfaceof an insulative distal member include the distal housing-based ringelectrode 22 (FIG. 7), the distal housing-based ring electrode extendingcircumferentially around the assembly 36 (FIG. 7), button electrodes,other housing-based electrodes, and other circumferential ringelectrodes. Any non-tissue piercing electrodes directly coupled to adistal insulative member, peripherally to a central tissue-piercingelectrode, may be provided to function individually, collectively, or inany combination as a cathode electrode for delivering pacing pulses toadjacent cardiac tissue. When a ring electrode, such as the distal ringelectrode 22 and/or a circumferential ring electrode, is provided,portions of the ring electrode may be electrically insulated by acoating to provide multiple distributed non-tissue piercing electrodesalong the distal-facing surface and/or the circumferential surface ofthe insulative distal member.

The non-tissue piercing electrodes 722 and other examples listed aboveare expected to provide more reliable and effective atrial pacing andsensing than a tissue-piercing electrode provided along the distalfixation and electrode assembly 736. The atrial chamber walls arerelatively thin compared to ventricular chamber walls. A tissue-piercingatrial cathode electrode may extend too deep within the atrial tissueleading to inadvertent sustained or intermittent capture of ventriculartissue. A tissue-piercing atrial cathode electrode may lead tointerference with sensing atrial signals due to ventricular signalshaving a larger signal strength in the cardiac electrical signalreceived via tissue-piercing atrial cathode electrodes that are incloser physical proximity to the ventricular tissue. The tissue-piercingelectrode assembly 712 may be securely anchored into ventricular tissuefor stabilizing the implant position of the device 710 and providingreasonable certainty that the tip electrode 742 is sensing and pacing inventricular tissue while the non-tissue piercing electrodes 722 arereliably pacing and sensing in the atrium. When the device 710 isimplanted in the target implant region 4, e.g., as shown in FIG. 1 theventricular septum, the tip electrode 742 may reach left ventriculartissue for pacing of the left ventricle while the non-tissue piercingelectrodes 722 provide pacing and sensing in the right atrium. Thetissue-piercing electrode assembly 712 may be in the range of about 4 toabout 8 mm in length from the distal-facing surface 738 to reach leftventricular tissue. In some instances, the device 710 may achievefour-chamber pacing by delivering atrial pacing pulses from the atrialpacing circuit 83 via the non-tissue piercing electrodes 722 in thetarget implant region 4 to achieve bi-atrial (right and left atrial)capture and by delivering ventricular pacing pulses from the ventricularpacing circuit 85 via the tip electrode 742 advanced into ventriculartissue from the target implant region 4 to achieve biventricular (rightand left ventricular) capture.

FIG. 10 shows an illustrative method 600 of detecting atrial activity,for example, using the acoustic or motion detector 11 of FIG. 5, whichmay be used to represent physiological response information. Inparticular, method 600 may include detecting an atrial contraction basedon analysis of a motion signal (e.g., provided by the motion detector11) that may be performed by an IMD implanted in the patient's heart. Insome embodiments, the motion signal may be provided by an IMD implantedwithin a ventricle, such as the right ventricle, of the patient's heart.The method 600 may include beginning an atrial contraction detectiondelay period upon identification of a ventricular activation event 630.The method 600 may include beginning an atrial contraction detectionwindow upon expiration of the atrial contraction delay period 632. Themethod 600 may include analyzing the motion signal within the atrialcontraction detection window.

The method 600 may include filtering the motion signal within the atrialcontraction detection window, rectifying the filtered signal, andgenerating a derivative signal of the filtered and rectified motionsignal 634 within the atrial contraction detection window. The method600 may include determining whether an amplitude of the derivativesignal within the atrial contraction detection window exceeds athreshold 636. In response to determining that the amplitude of thederivative signal within the atrial contraction detection window exceedsthe threshold (YES of 636), the method 600 may proceed to detectingatrial contraction 638. Otherwise (NO of 636), the method 600 may returnto filtering, rectifying, and generating a derivative signal 634.Various techniques for using a motion detector that provides a motionsignal may be described in U.S. Pat. No. 9,399,140 (Cho et al.), issuedJul. 26, 2016, entitled “Atrial contraction detection by a ventricularleadless pacing device for atrio-synchronous ventricular pacing,” whichis incorporated herein by reference in its entirety.

As will be described with respect to FIG. 11, heart sounds (HS) may bedetected and used to represent physiological response information.described herein, the amplitudes and/or relative time intervals of oneor more of the S1 through S4 heart sounds can be useful in optimizing apatient's hemodynamic response to CRT or other cardiac therapies thatinclude cardiac pacing and/or neural stimulation for achievinghemodynamic benefit. The first heart sound, S1, corresponds to the startof ventricular systole. Ventricular systole begins when an actionpotential conducts through the atrioventricular node (AV node) andquickly depolarizes the ventricular myocardium. This event isdistinguished by the QRS complex on the ECG. As the ventricles contract,pressure in the ventricles begins to rise, causing abrupt closure of themitral and tricuspid valves between the ventricles and atria asventricular pressure exceeds atrial pressure. This valve closure maygenerate S1. S1 generally has a duration of about 150 ms and a frequencyon the order of about 20 to 250 Hz. The amplitude of S1 may provide asurrogate measurement of LV contractility. Thus, an increase in S1amplitude positively may correlate with an improvement in LVcontractility. Other measures, like pre-ejection period measured fromonset of QRS to S1, may be also used as a surrogate of myocardialcontractility index.

Separation of the closure of the mitral and tricuspid valves due toventricular dyssynchrony can be observed as separate M1 and T1 peaks inthe S1 signal. Merging of the M1 (mitral valve closure sound) and the T1(tricuspid valve closure sound) can be used as an indication of improvedventricular synchrony.

Generally, left ventricular pressure (LVP) rises dramatically followingthe QRS complex of the ECG and closure of the mitral valve and continuesto build during ventricular systole until the aortic and pulmonaryvalves open, ejecting blood into the aorta and pulmonary artery.Ventricular contraction typically continues to cause blood pressure torise in the ventricles and the aorta and pulmonary artery during theejection phase. As the contraction diminishes, blood pressure decreasesuntil the aortic and pulmonary valves close.

The second heart sound, S2, may be generated by the closure of theaortic and pulmonary valves, near the end of ventricular systole andstart of ventricular diastole. S2 may therefore be correlated todiastolic pressure in the aorta and the pulmonary artery. S2 generallyhas a duration of about 120 ms and a frequency on the order of 25 to 350Hz. The time interval between S1 and S2, i.e., S1-S2 time interval, mayrepresent the systolic time interval (STI) corresponding to theventricular isovolumic contraction (pre-ejection) and ejection phase ofthe cardiac cycle. This S1-S2 time interval may provide a surrogatemeasurement for stroke volume. Furthermore, the ratio of pre-ejectionperiod (Q-S1) to S1-S2 time may be used as an index of myocardialcontractility.

The third heart sound, S3, is associated with early, passive diastolicfilling of the ventricles, and the fourth heart sound, S4, may beassociated with late, active filling of the ventricles due to atrialcontraction. The third sound is generally difficult to hear in a normalpatient using a stethoscope, and the fourth sound is generally not heardin a normal patient. Presence of the third and fourth heart soundsduring an examination using a stethoscope may indicate a pathologicalcondition. The S3 and S4 heart sounds may be used in optimizing paceparameters as they relate to diastolic function of the heart. Generally,these sounds would be minimized or disappear when an optimal paceparameter is identified. Other aspects of the S1 through S4 heart soundsand timing thereof that may be useful in cardiac pace parameteroptimization as known to one having ordinary skill in the art.

FIG. 11 is a flow chart 800 of a method for using heart sounds tooptimize pace control parameters according to one embodiment. Methods ofthe present disclosure may include one or more blocks shown in flowchart 800. Other examples of using heart sounds to optimize cardiactherapy are described generally in U.S. Pat. No. 9,643,0134, granted May9, 2017, entitled “System and method for pacing parameter optimizationusing heart sounds,” which is incorporated herein by reference in itsentirety.

A pace parameter optimization method may be initiated at block 802. Theoptimization process may be initiated in response to a user commandreceived via an external programmer. At a time of initial IMDimplantation or during office follow-up visits, or during a remotepatient monitoring session, a user may initiate a HS-base optimizationprocedure using an external programmer or networked computer.Additionally, or alternatively, the process shown by flow chart 800 maybe an automated process started periodically or in response to sensing aneed for therapy delivery or therapy adjustment based on a sensedphysiological signal, which may include sensed HS signals.

At block 804 a pace control parameter to be optimized is selected. Acontrol parameter may be a timing-related parameter, such as AV intervalor VV interval. Pacing vector is another control parameter that may beselected at block 804 for optimization. For example, when a multi-polarlead is used, such as a coronary sinus lead, multiple bipolar orunipolar pacing vectors may be selected for pacing in a given heartchamber. The pacing site associated with a particular pacing vector mayhave a significant effect on the hemodynamic benefit of a pacingtherapy. As such, pacing vector is one pace control parameter that maybe optimized using methods described herein.

A pacing sequence is initiated at block 806 using an initial parametersetting for the test parameter selected at block 804. In one embodiment,the AV interval is being optimized, and ventricular pacing is deliveredat an initial AV interval setting. It is understood that an initial AVinterval setting may be selected at block 806 by first measuring anintrinsic AV interval in a patient having intact AV conduction, i.e. noAV block. An initial AV interval may be a default pacing interval, thelast programmed AV interval, or a minimum or maximum AV interval to betested. Alternatively, if the VV interval is selected for optimization,an intrinsic inter-ventricular conduction time may be measured first andpaced VV intervals may be iteratively adjusted beginning at a VVinterval longer, shorter or approximately equal to the intrinsic VVconduction time.

An iterative process for adjusting the selected test parameter to atleast two different settings is performed. The parameter may be adjustedto different settings in any desired order, e.g., increasing,decreasing, random etc. For example, during adjustment of AV interval,an initial AV interval may be set to just longer than or approximatelyequal to a measured intrinsic AV conduction time then iterativelydecreased down to a minimum AV interval test setting. During pacingusing each pace parameter setting, HS signals are acquired at block 808.The iterative process advances to the next test parameter setting atblock 812 until all test parameter settings have been applied, asdetermined at block 810, and HS signals have been recorded for eachsetting.

HS signals may be acquired for multiple cardiac cycles to enableensemble averaging or averaging of HS parameter measurements taken fromindividual cardiac cycles. It is understood that amplification,filtering, rectification, noise cancellation techniques or other signalprocessing steps may be used for improving the signal-to-noise ratio ofthe HS signals and these steps may be different for each of the heartsounds being acquired, which may include any or all types of heartsounds.

At least one HS parameter measurement is determined from the recorded HSsignals for each test parameter setting at block 814. The IMD processoror an external processor, e.g. included in a programmer, or acombination of both may perform the HS signal analysis described herein.In one embodiment, S1 and S2 are recorded and HS parameters are measuredusing the S1 and S2 signals at block 814. For example, the amplitude ofS1, the V-S2 interval (where the V event may be a V pace or a sensedR-wave), and the S1-S2 interval are measured. The presence of S3 and/orS4 may additionally be noted or measurements of these signals may bemade for determining related parameters. HS signal parameters aredetermined for at least two different test parameter settings, e.g. atleast two different AV intervals, two or more different VV intervals, ortwo or more different pacing vectors.

At block 818, a trend for each HS parameter determined at block 810 as afunction of the pace parameter test settings is determined. In oneembodiment, a trend for each of the V-S2 interval, S1 amplitude andS1-S2 interval is determined. Other embodiments may include determininga separation of the M1 and T1 sounds during the S1 signal. Based on thetrends of the HS parameter(s) with respect to the varied pace controlparameter, an optimal pace parameter setting may be identifiedautomatically by the processor at block 820. Additionally,alternatively, and/or optionally the HS trends are reported anddisplayed at block 822 on an external device such as programmer or at aremote networked computer.

If the pace parameter being tested is, for example, pacing site orpacing vector when a multipolar electrode is positioned along a heartchamber, such as a quadripolar lead along LV, a pacing site or vectormay be selected based on maximizing a HS-based surrogate for ventricularcontractility. In one embodiment, the amplitude of S1 is used as asurrogate for ventricular contractility, and a pacing site or vectorassociated with a maximum S1 is identified at block 820 as the optimalpacing vector setting.

Determining the trend of each HS parameter at block 818 may includedetermining whether the V-S2 interval trend presents a sudden slopechange, e.g. from a substantially flat trend to a decreasing trend. AnAV interval associated with a sudden change in the V-S2 interval trendmay be identified as an optimal AV interval setting. The optimal AVinterval may be further identified based on other HS trends, for examplea maximum S1 amplitude and/or a maximum S1-S2 interval.

In some embodiments, an automatically-identified optimal pace parametersetting may also be automatically programmed in the IMD at block 824. Inother embodiments, the clinician or user reviews the reported HS dataand recommended pace parameter setting(s) and may accept a recommendedsetting or select another setting based on the HS data.

HS sensing module, or circuitry, may be operably coupled to the controlcircuit 80 (FIG. 8) and be configured to receive analog signals from anHS sensor for sensing one or more of these heart sounds. For example,the HS sensing module may include one or more “channels” configured toparticularly sense a specific heart sound based on frequency, duration,and timing of the heart sounds. For example, ECG/EGM sensing circuitrymay be used by the control circuit 80 to set HS sensing windows used byHS sensing module for sensing the heart sounds. HS sensing module mayinclude one or more sense amplifiers, filters and rectifiers foroptimizing a signal to noise ratio of heart sound signals. Separate andunique amplification and filtering properties may be provided forsensing each of the S1 through S4 sounds to improve signal quality asneeded.

Bioimpedance, or intracardiac impedance, may be measured and used torepresent physiological response information. For example, any of theIMDs described herein may measure an intracardiac impedance signal byinjecting a current and measuring a voltage between electrodes of anelectrode vector configuration (e.g., selected electrodes). For example,the IMD may measure an impedance signal by injecting a current (e.g., anon-pacing threshold current) between a first electrode (e.g., LVelectrode) and an electrode located in the RA and measuring a voltagebetween the first and second electrodes. One will recognize that othervector pair configurations may be used for stimulation and measurement.Impedance can be measured between any set of electrodes that encompassthe tissue or cardiac chamber of interest. Thus, one can inject currentand measure voltage to calculate the impedance on the same twoelectrodes (a bipolar configuration) or inject current and measurevoltage on two separate pairs of electrodes (e.g., one pair for currentinjection and one pair for voltage sense), hence, a quadripolarconfiguration. For a quadripolar electrode configuration, the currentinjection and voltage sense electrodes may be in line with each other(or closely parallel to) and the voltage sense electrodes may be withinthe current sense field. In such embodiments, a VfA lead may be used forthe LV cardiac therapy or sensing. The impedance vectors can beconfigured to encompass a particular anatomical area of interest, suchas the atrium or ventricles.

The exemplary methods and/or devices described herein may monitor one ormore electrode vector configurations. Further, multiple impedancevectors may be measured concurrently and/or periodically relative toanother. In at least one embodiment, the exemplary methods and/ordevices may use impedance waveforms to acquire selection data (e.g., tofind applicable fiducial points, to allow extraction of measurementsfrom such waveforms, etc.) for optimizing CRT.

As used herein, the term “impedance signal” is not limited to a rawimpedance signal. It should be implied that raw impedance signals may beprocessed, normalized, and/or filtered (e.g., to remove artifacts,noise, static, electromagnetic interference (EMI), and/or extraneoussignals) to provide the impedance signal. Further, the term “impedancesignal” may include various mathematical derivatives thereof includingreal and imaginary portions of the impedance signal, a conductancesignal based on the impedance (i.e., the reciprocal or inverse ofimpedance), etc. In other words, the term “impedance signal” may beunderstood to include conductance signals, i.e. signals that are thereciprocal of the impedance signal.

In one or more embodiments of the methods and/or devices describedherein, various patient physiological parameters (e.g., intracardiacimpedance, heart sounds, cardiac cycle intervals such as R-R interval,etc.) may be monitored for use in acquiring selection data to optimizeCRT (e.g., set AV and/or VV delay, optimize cardiac contractility, forexample, by using and/or measuring impedance first derivative dZ/dt,select pacing site, select pacing vector, lead placement, or assesspacing capture from both the electrical and mechanical points of view(e.g., electrical capture may not mean mechanical capture, and the heartsounds and impedance may assist in assessing whether the electricalstimulus captures the heart or not by looking at the mechanicalinformation from the heart sounds and impedance), select an effectiveelectrode vector configuration for pacing, etc.). For example,intracardiac impedance signals between two or more electrodes may bemonitored for use in providing such optimization.

FIG. 12 shows one example of a method 850 for acquiring selection datafor one of the device parameter options (e.g., one of the selectabledevice parameters that may be used to optimize CRT, such as a potentialAV delay that may be an optimal parameter). Other examples of usingheart sounds to optimize cardiac therapy are described generally in U.S.Pat. No. 9,707,399, granted Jul. 18, 2017, entitled “Cardiacresynchronization therapy optimization based on intracardiac impedanceand heart sounds,” which is incorporated herein by reference in itsentirety.

As shown, pacing therapy is delivered using one of the plurality ofdevice options (block 852) (e.g., the plurality of device parameteroptions may be selected, determined and/or calculated AV delays, such aspercentages of intrinsic AV delay, for example, 40% of intrinsic AVdelay, 50% of intrinsic AV delay, 60% of intrinsic AV delay, 70% ofintrinsic AV delay, 80% of intrinsic AV delay, etc.). For the deviceparameter option used to pace (block 852), selection data is acquired ateach of a plurality of electrode vector configurations (e.g.,intracardiac impedance is monitored over a plurality of cardiac cyclesand selection data is extracted using such impedance signal). Asindicated by the decision block 854, if selection data has not beenacquired from all desired electrode vector configurations, then the loopof acquiring selection data (e.g., the loop illustrated by blocks 858,860, 862, and 864) is repeated. If selection data has been acquired fromall desired electrode vector configurations, then another differentdevice parameter option is used to deliver therapy (block 856) and themethod 850 of FIG. 12 is repeated (e.g., for the different deviceparameter option) until selection data has been acquired for all thedifferent device parameter options (e.g., selection data being collectedat each of a plurality of electrode vector configurations for each ofthe different device parameter options).

As shown in the repeated loop of acquiring selection data for each ofthe desired electrode vector configurations (e.g., blocks 858, 860, 862,and 864), one of the plurality of electrode vector configurations isselected for use in acquiring selection data (block 858). Temporalfiducial points associated with at least a part of a systolic portion ofat least one cardiac cycle and/or temporal fiducial points associatedwith at least a part of a diastolic portion of at least one cardiaccycle for the selected electrode vector configuration are acquired(block 860) (e.g., such as with use of heart sounds, analysis ofimpedance signal minimum and maximums, application of algorithms basedon physiological parameters such as R-R intervals, etc.). For example,temporal fiducial points associated with the systolic and/or diastolicportions of the cardiac cycle may be acquired, temporal fiducial pointsassociated with one or more defined segments within systolic and/ordiastolic portions of the cardiac cycle may be acquired, and/or temporalfiducial points within or associated with one or more points and/orportions of a systolic and/or diastolic portion of the cardiac cycle maybe acquired. Yet further, for example, temporal fiducial pointsassociated with just the systolic portion or just the diastolic portionof the cardiac cycle may be acquired, temporal fiducial pointsassociated with one or more defined segments within just the systolicportion or just the diastolic portion of the cardiac cycle may beacquired, and/or temporal fiducial points within or associated with oneor more points and/or portions of just the systolic portion or just thediastolic portion of the cardiac cycle may be acquired. In other words,fiducial points may be acquired that are associated with either both thesystolic and diastolic portions of the cardiac cycle or associated withjust one of such portions of the cardiac cycle. Further, for example,such fiducial points may be representative or indicative of ameasurement window and/or time period (e.g., interval, point, etc.) ator during which intracardiac impedance may be measured for use inanalysis as described herein.

In about the same timeframe (e.g., about simultaneously with theacquired fiducial points), an intracardiac impedance signal is acquiredat the selected electrode vector configuration (block 862). With theacquired fiducial points and the acquired intracardiac impedance signal,measurements from the impedance signal are extracted based on thetemporal fiducial points (block 864) (e.g., integral of the impedancesignal in a measurement window defined between fiducial points, maximumslope of impedance signal in a measurement window defined betweenfiducial points, time between the fiducial points, maximum impedance ata fiducial point, etc.). One or more of such measurements may becomparable to desired values for such measurements allowing for adetermination of whether the measurement may indicate that the deviceparameter option may be an effective device parameter for optimizingtherapy (e.g., a scoring algorithm may be used to determine if a deviceparameter option may be an optimal parameter based on whether aplurality of such measurements meet certain criteria or thresholds).

The measurement data for each of the device parameter options (e.g.,obtained such as described in FIG. 12) is determined for at least onecardiac cycle. In one or more embodiments, such measurement data isacquired for a plurality of cardiac cycles. The cardiac cycles duringwhich measurement data is acquired may be any suitable cardiac cycle. Inone or more embodiments, the selected cardiac cycles during whichmeasurement data is acquired is based on the respiratory cycle. In atleast one embodiment, the measurement data is acquired during cardiaccycles occurring at the end of a respiratory cycle (e.g., proximate theend of expiration).

An illustrative method 200 for monitoring effectiveness of leftventricular capture for use with, e.g., the illustrative systems anddevices of FIGS. 1-5 and 7-9, is depicted in FIG. 13. In particular, themethod 200 may be used with an illustrative VfA device shown anddescribed herein delivering cardiac resynchronization therapy to a heartof a patient. For example, the VfA devices may deliver DDD(R), VVI(R),or VVI cardiac therapies. Thus, a left ventricular pace may be deliveredusing the tissue-piercing electrode that implanted from the triangle ofKoch region of the right atrium through the right atrial endocardium andcentral fibrous body to deliver cardiac therapy to and/or senseelectrical activity of the left ventricle in the basal and/or septalregion of the left ventricular myocardium of a patient's heart.

As shown, the method 200 includes monitoring effectiveness of leftventricular capture 210, determining whether effective or ineffectiveleft ventricular capture exits 220, and adjusting the left ventricularpacing 230 if it is determined that the left ventricular pacing is noteffective or is ineffective. As shown, the method 200 may continue toloop or be executed periodically to provide continuous monitoring ofeffectiveness of left ventricular capture. For example, monitoringeffectiveness 210 may be continuously performed while determiningwhether effective or ineffective left ventricular capture exits 220 maybe performed periodically or intermittently. Further, for example,monitoring effectiveness 210 may be continuously performed anddetermining whether effective or ineffective left ventricular captureexits 220 may be performed on the most current selected period of time(e.g., the last 10 cardiac cycles).

A more detailed flow diagram of one embodiment of method 200 depicted inFIG. 13 is shown in FIG. 15. As shown, monitoring effectiveness of leftventricular capture 210 may include delivering a left ventricular pace212. The timing of the left ventricular pace, as well as whether theleft ventricular pace is delivered (e.g., in the case of an early leftventricular activation), may depend on the therapy being delivered but,nonetheless, the electrical activity following the pace may be monitored214. It is be understood that in this example, while the electricalactivity is monitored and used to determine left ventricular capture,any other form of physiological data may be acquired to determine and/orevaluate effective left ventricular capture such as motion sensing orimpedance sensing.

In particular, a selected period of time, selected time period, or timewindow, 254 following a left ventricular pace may be monitored using anear-field signal. For example, the near-field signal may be monitoredusing two or more electrodes of the VfA device. In particular, thetissue-piercing electrode implanted from the triangle of Koch region ofthe right atrium through the right atrial endocardium and centralfibrous body may be one of the two electrodes. Another electrode may bea right atrial electrode positioned in the right atrium of the patient.In one embodiment, the right atrial electrode may be positioned incontact with the right atrial septum or other atrial tissue, and inanother embodiment, the right atrial electrode may be positioned in theright atrium without contacting the right atrial tissue (e.g., “freefloating” in the right atrium). Nonetheless, the electrical signalmonitored may be referred to as a near-field signal because, e.g., thesignal is not monitored using any electrodes positioned outside or faraway from the heart.

The selected period of time, selected time, period, or time window, 254following the left ventricular pace may be between about 40 millisecondsand about 150 milliseconds. In one embodiment, the selected period oftime is about 84 milliseconds.

The electrogram of the near-field signal over the selected period oftime may be evaluated using one or more various metrics or comparisons.For example, various morphological features and timings of suchmorphological features may be analyzed. In particular, one or more ofamplitudes at baseline immediately before or at the time of delivery ofpacing, minimum values of amplitude relative to the baseline amplitude,maximum values relative to the baseline amplitude, times of occurrenceof the minimum value, minimum or maximum values occurring first or last,minimum or maximum values occurring during selected durations orfollowing other events, slopes (first derivatives), second derivatives,absolute minimums or maximums, etc. may be used to analyze thenear-field electrogram for use in determining effective capture of theleft ventricle.

A portion of illustrative monitored near-field electrogram 250 followinga ventricular pace for use in determining effectiveness of leftventricular capture is depicted in FIG. 14. In this example, multiplemorphological features and morphological feature timings are identifiedwhich may be used to determine effectiveness of left ventricular captureof the left ventricular pacing therapy 216.

The absolute baseline amplitude 251 may be used to determineeffectiveness of left ventricular capture of the left ventricular pacingtherapy 216. The baseline amplitude 251 may be defined as the amplitudeimmediately before or at the time pace is delivered. The absolutebaseline amplitude 251 may be compared to an absolute baseline thresholdvalue. The absolute baseline threshold value may be between about 0millivolts and about 1 millivolts. In one embodiment, the absolutebaseline threshold value is 0.63 millivolts. If the absolute baselineamplitude 251 is less than the absolute baseline threshold, then it maybe determined that effective left ventricular capture is occurring.

The minimum negative deflection 252 within a selected negativedeflection time period may be used to determine effectiveness of leftventricular capture of the left ventricular pacing therapy 216. Inparticular, the minimum negative deflection 252 may be compared to aminimum threshold value. The minimum threshold value may be betweenabout 1 millivolts and about 10 millivolts. In one embodiment, theminimum threshold value is 1 millivolts. If the minimum negativedeflection 252 is less than the minimum threshold (in other words, morenegative than the minimum threshold), then it may be determined thateffective left ventricular capture is occurring.

Additionally, as mentioned, the minimum negative deflection 252 isevaluated within, or taken from, a selected negative deflection timeperiod. The selected negative deflection time period may be betweenabout 40 milliseconds and about 100 milliseconds following the leftventricular pace. In one embodiment, the selected negative deflectiontime period is 84 milliseconds.

The time period between the left ventricular pace and the minimumnegative deflection, or the timing of the minimum negative deflection,253 may be used to determine effectiveness of left ventricular captureof the left ventricular pacing therapy 216. In particular, the timeperiod between the left ventricular pace and the minimum negativedeflection 253 may be compared to an interval threshold. The intervalthreshold may be between about 40 milliseconds and about 60milliseconds. In one embodiment, the interval threshold is 45milliseconds. If the time period between the left ventricular pace andthe minimum negative deflection 253 is less than the interval threshold,then it may be determined that effective left ventricular capture isoccurring.

The relative order of occurrence of the maximum amplitude and minimumamplitude within the selected time period 254 may be used to determineeffectiveness of left ventricular capture of the left ventricular pacingtherapy 216. For example, if the occurrence, or timing, of the minimumamplitude precedes, or occurs before, the occurrence, or timing, of themaximum amplitude, then it may be determined that effective leftventricular capture is occurring. In other words, if a minimum negativedeflection of the monitored electrical activity occurs prior to amaximum positive deflection of the monitored electrical activity, thenit may be determined that effective left ventricular capture isoccurring. In one embodiment, a negative, or minimum, deflection timestamp corresponding to the minimum negative deflection or amplitude maybe compared to a positive, or maximum, deflection time stampcorresponding to the maximum positive deflection or amplitude.

As such, four illustrative criteria or metrics are described herein foruse in determining effectiveness of left ventricular capture of a leftventricular pace. These four illustrative criteria or metrics may beeach used by themselves or in conjunction with each other. For example,a pace may be determined to have effectively captured the left ventricleif all four of the illustrative criteria have been met. In otherembodiments, meeting less than all four criteria such as two of the fouror three of the four criteria may indicate effective capture.

Thus, the effectiveness of capture of the left ventricular pace may bedetermined 216, and the method or process 210 may continuously loop (asindicated by the arrow extending form the process 216 to process 212)thereby monitoring and evaluating the capture of each left ventricularpace. In effect, an amount of effective left ventricular paces may becounted over a plurality of paced and/or intrinsic (e.g., unpaced) heartbeats depending on the particular cardiac therapy being delivered. Sucha count over an elapsed time period (e.g., one day or longer, a week orlonger, device life-time, time period since last device interrogation,etc.) may be expressed on a device programmer interface as a diagnosticof effective left ventricular pacing.

The exemplary method 200 may further adjust the left ventricular pacing230 if it is determined that the left ventricular pacing does not haveeffective capture. Such determination to adjust may occur over aplurality of paces or cardiac cycles to, e.g., eliminate anomalies, etc.

Further, different therapies may have different kinds of adjustments ofleft ventricular pacing therapy for improving effective capture overtime. As shown in FIG. 15, in DDD(r) cardiac therapy, a number, n, ofeffective left ventricular paces over a number, m, of cardiac cycles 222may be used to determine whether effective left ventricular capture isoccurring. In other words, a determination of whether a first amount ofleft ventricular paces has not achieved effective left ventriculartissue capture over a second amount of cardiac cycles may be executed.

Thus, evaluation of the effectiveness of left ventricular pacing over aplurality of cardiac cycles may be used to determine whether to adjustpacing in DDD(r) cardiac therapy. This metric may be described as being“rolling” such that it may evaluate the previous m cardiac cycles on acontinual basis. Additionally, process 222 may be described in terms ofa selected percentage of effective left ventricular paces over the pastm cardiac cycles. For example, if at least 90 left ventricular paces aredetermined to be effective over the past 100 left ventricular pacedcardiac cycles, then it may be determined that the DDD(r) cardiactherapy has effective left ventricular capture and does not needadjustment. Conversely, if less than 90 left ventricular paces aredetermined to be effective over the past 100 left ventricular pacedcardiac cycles, then it may be determined that the DDD(r) cardiactherapy does not have adequate left ventricular capture and should beadjusted 232.

For instance, the left ventricular pacing amplitude may be increased 232by a selected value or a selected percentage. The selected value may bebetween about 0.25 millivolts and about 1 millivolts. In one embodiment,the selected value is 0.5 millivolts. Additionally, the left ventricularpacing amplitude may be increased until a threshold, limit, or boundaryis reached. In other words, an upper threshold may be used such that theamplitude may be increased until it reaches the upper threshold. Theupper threshold may be between 4 mV and 10 mV. In one embodiment, theupper threshold is 6 about mV.

In other embodiments, instead of or in conjunction with increasingpacing amplitude, one or more other pacing settings may be increased oradjusted such as pulse width, pulse frequency, etc.

Further, the A-V delay may be adjusted 232. As used herein, the term“A-V delay” or “AV pacing interval” refers to a determined delay betweenatrial activation (As or Ap) and timing of delivery of ventricularpacing (Vp), wherein the atrial activation may include an intrinsicatrial activation (As), or atrial sense, or a paced atrial activation(Ap). Specifically, the A-V delay (which may include a plurality ofdifferent A-V delays corresponding to a plurality of differentheartrates) may be decreased by a selected amount or selectedpercentage. For example, the A-V delay may be decreased by 10milliseconds until effective left ventricular is captured or a lowerbound is reached such as, e.g., 60 milliseconds for As and 70milliseconds for Ap. Further, for example, the A-V delay may bedecreased by 5% until effective left ventricular is captured or a lowerbound is reached.

In some embodiments, the amplitudes, A-V delays, and other pacedsettings may be adjusted 232 until left ventricular capture is obtained,which may be determined using the same or similar processes asmonitoring the effectiveness of left ventricular capture 210. After theleft ventricular pacing has been adjusted to achieve effective capture,the method may return to monitoring the effectiveness of leftventricular capture 210. Additionally, it is be understood thatmonitoring the effectiveness of left ventricular capture 210 may beoccurring continuously even while other processes of the method arebeing executed. In other words, monitoring the effectiveness of leftventricular capture 210 may be a permanent process that is alwaysrunning.

Further as shown in FIG. 15, in VVI(r) cardiac therapy, a number, n, ofeffective left ventricular paces and a number, x, of effective intrinsicleft ventricular activated over a number, m, of cardiac cycles may beused to determine 224 whether effective left ventricular capture isoccurring. In other words, a determination of whether a first amount ofleft ventricular paces have not achieved effective left ventriculartissue capture over a second amount of cardiac cycles and adetermination of whether a third amount of intrinsic left ventricularactivations have been sensed over the second amount of cardiac cyclesmay be executed.

Thus, evaluation of the effectiveness of a left ventricular pace andintrinsic activity over a plurality of cardiac cycles may be used todetermine whether to adjust pacing in VVI(r) cardiac therapy. Thismetric, similar to those used in DDD(r) therapy, may be described asbeing “rolling.”

For example, if at least 90 left ventricular paces are determined to beeffective over the past 100 cardiac cycles including paced and intrinsiccardiac cycles, then it may be determined that the VVI(r) cardiactherapy has effective left ventricular capture and does not needadjustment. Conversely, if less than 90 left ventricular paces and if atleast 10 intrinsic left ventricular activation are determined to beeffective over the past 100 cardiac cycles, then it may be determinedthat the VVI(r) cardiac therapy does not have adequate left ventricularcapture and should be adjusted 234. Additionally, process 224 may bedescribed in terms of a selected percentage of effective leftventricular paces over the past m cardiac cycles and a selectedpercentage of effective intrinsic activations over the past m cardiaccycles.

The adjustment of the VVI(r) cardiac therapy may include adjusting theheart rate 232 using, e.g., a heart rate delay. For example, the heartrate delay, or LV-LV timing, may be decreased to obtain an increase inheartrate by, e.g., 10 beats per minute, until either effective leftventricular capture is obtained or a limit is reached such as, e.g., 130beats per minute. In other embodiments, the heart rate delay may bedecreased by a selected percentage until either effective leftventricular capture is obtained or a limit is reached. After the leftventricular pacing has been adjusted to achieve effective capture, themethod may return to monitoring the effectiveness of left ventricularcapture 210.

Still further, in VVI cardiac therapy, a number, n, of effective leftventricular paces over a number, m, of cardiac cycles and whether or notany intrinsic left ventricular activated were sensed over a number, m,of cardiac cycles 226 may be used to determine whether effective leftventricular capture is occurring. In other words, a determination 226 ofwhether a first amount of left ventricular paces have not achievedeffective left ventricular capture and a determination that no intrinsicleft ventricular activations have been sensed may be executed.

Thus, evaluation of the effectiveness of a left ventricular pace andintrinsic activity over a plurality of cardiac cycles may be used todetermine whether to adjust pacing in VVI cardiac therapy. This metric,similar to those used in DDD(r) therapy, may be described as being“rolling.”

For example, if at least 90 left ventricular paces are determined to beeffective over the past 100 cardiac cycles, then it may be determinedthat the VVI cardiac therapy has effective left ventricular capture anddoes not need adjustment. Conversely, if less than 90 left ventricularpaces are determined to be effective and no intrinsic left ventricularactivation have been sensed over the past 100 cardiac cycles, then itmay be determined that the VVI cardiac therapy does not have adequateleft ventricular capture and should be adjusted 236. The adjustment 236of the VVI cardiac therapy may include adjusting pacing output includingpacing amplitude and/or another paced setting which may be similar tothe adjustment process 232 described herein with respect to DDD(r)pacing. After the left ventricular pacing has been adjusted to achieveeffective capture, the method may return to monitoring the effectivenessof left ventricular capture 210.

Additionally, an alert may be issued if ineffective left ventriculartissue capture is determined by one or more processes as show in FIGS.13 and 15. For example, an implantable medical device may issue an alertto external devices such as a smartphone, other medical device, or areader. Further, for example, a sound may be emitted from one or more ofsaid devices thereby alerting the user.

Illustrative Embodiments

Embodiment 1: An implantable medical device comprising:

a plurality of electrodes comprising:

-   -   a tissue-piercing electrode implantable from the triangle of        Koch region of the right atrium through the right atrial        endocardium and central fibrous body to deliver cardiac therapy        to or sense electrical activity of the left ventricle in the        basal and/or septal region of the left ventricular myocardium of        a patient's heart, and    -   right atrial electrode positionable within the right atrium to        deliver cardiac therapy to or sense electrical activity of the        right atrium of the patient's heart;

a therapy delivery circuit operably coupled to the plurality ofelectrodes to deliver cardiac therapy to the patient's heart;

a sensing circuit operably coupled to the plurality of electrodes tosense electrical activity of the patient's heart; and

a controller comprising processing circuitry operably coupled to thetherapy delivery circuit and the sensing circuit, the controllerconfigured to monitor effectiveness of left ventricular capture by:

operating the therapy delivery circuit to deliver a left ventricularpace using the tissue-piercing electrode;

monitoring, via the sensing circuit, electrical activity of the leftventricle using the tissue-piercing electrode following the leftventricular pace; and

determining effectiveness of left ventricular tissue capture of the leftventricular pace based on the monitored electrical activity.

Embodiment 2: A method comprising:

providing a tissue-piercing electrode implanted from the triangle ofKoch region of the right atrium through the right atrial endocardium andcentral fibrous body to deliver cardiac therapy to or sense electricalactivity of the left ventricle in the basal and/or septal region of theleft ventricular myocardium of a patient's heart;

providing a right atrial electrode positionable within the right atriumto deliver cardiac therapy to or sense electrical activity of the rightatrium of the patient's heart;

delivering a left ventricular pace using the tissue-piercing electrode;

monitoring electrical activity of the left ventricle using thetissue-piercing electrode following the left ventricular pace; and

determining effectiveness of left ventricular tissue capture of the leftventricular pace based on the monitored electrical activity.

Embodiment 3: The embodiment as in any one of embodiments 1-2, whereinmonitoring electrical activity of the left ventricle using thetissue-piercing electrode following the left ventricular pace comprisesmonitoring electrical activity of the left ventricle using thetissue-piercing electrode and the right atrial electrode.

Embodiment 4: The embodiment as in any one of embodiments 1-3, whereindetermining effectiveness of left ventricular tissue capture of the leftventricular pace based on the monitored electrical activity comprisescomparing an absolute baseline amplitude of the monitored electricalactivity to an absolute baseline amplitude threshold.

Embodiment 5: The embodiment as in any one of embodiments 1-4, whereindetermining effectiveness of left ventricular tissue capture of the leftventricular pace based on the monitored electrical activity comprisescomparing a minimum negative deflection within a selected time periodfollowing the left ventricular pace to a minimum threshold.

Embodiment 6: The embodiment as in any one of embodiments 1-5, whereindetermining effectiveness of left ventricular tissue capture of the leftventricular pace based on the monitored electrical activity comprisescomparing a time period between the left ventricular pace and a minimumnegative deflection to an interval threshold.

Embodiment 7: The embodiment as in any one of embodiments 1-6, whereindetermining effectiveness of left ventricular tissue capture of the leftventricular pace based on the monitored electrical activity comprisesdetermining whether a minimum negative deflection of the monitoredelectrical activity occurs prior to a maximum positive deflection of themonitored electrical activity.

Embodiment 8: The embodiment as in any one of embodiments 1-7, whereinthe controller is further configured to execute or the method furthercomprises:

monitoring effectiveness of left ventricular capture over a plurality ofcardiac cycles;

determining that effective left ventricular capture is not occurringbased on the monitored of effectiveness of left ventricular capture overthe plurality of cardiac cycles; and

adjusting left ventricular pacing in response to determining thateffective left ventricular capture is not occurring.

Embodiment 9: The embodiments as in embodiment 8, wherein determiningthat effective left ventricular capture is not occurring based on themonitored of effectiveness of left ventricular capture over theplurality of cardiac cycles comprises determining whether a first amountof left ventricular paces have not achieved effective left ventriculartissue capture over a second amount of cardiac cycles.

Embodiment 10: The embodiment as in any one of embodiments 8-9, whereinadjusting left ventricular pacing comprises adjusting one or both of aleft ventricular pacing amplitude of the left ventricular pace and adelay between an atrial sense or pace and the left ventricular paceuntil effective left ventricular tissue capture of the left ventricularpace is determined.

Embodiment 11: The embodiments as in embodiment 8, wherein determiningthat effective left ventricular capture is not occurring based on themonitored of effectiveness of left ventricular capture over theplurality of cardiac cycles comprises:

determining a first amount of left ventricular paces have not achievedeffective left ventricular tissue capture over a second amount ofcardiac cycles; and

determining a third amount of intrinsic left ventricular activationshave been sensed over the second amount of cardiac cycles.

Embodiment 12: The embodiments as in embodiment 11, wherein, in responseto determining that the first amount of left ventricular paces did notachieve effective left ventricular capture and that the third amount ofintrinsic left ventricular activations have been sensed, adjusting leftventricular pacing comprises:

adjusting a heart rate delay between a left ventricular sense or paceand the following left ventricular pace until effective left ventriculartissue capture of the left ventricular pace is determined.

Embodiment 13: The embodiments as in embodiment 11, wherein, in responseto determining that the first amount of left ventricular paces have notachieved effective left ventricular capture and that no intrinsic leftventricular activations have been sensed, adjusting left ventricularpacing comprises:

adjusting a left ventricular pacing amplitude of the left ventricularpace until effective left ventricular tissue capture of the leftventricular pace is determined.

Embodiment 14: The embodiment as in any one of embodiments 1-13, whereinthe controller is further configured to execute or the method furthercomprises issuing an alert if ineffective left ventricular tissuecapture is determined.

Embodiment 15: The embodiment as in any one of embodiments 1-14, whereinmonitoring effectiveness of left ventricular capture comprisesperiodically monitoring effectiveness of left ventricular capture over aselected amount of cardiac cycles.

Embodiment 16: An implantable medical device comprising:

a plurality of electrodes comprising:

-   -   a tissue-piercing electrode implantable from the triangle of        Koch region of the right atrium through the right atrial        endocardium and central fibrous body to deliver cardiac therapy        to or sense electrical activity of the left ventricle in the        basal and/or septal region of the left ventricular myocardium of        a patient's heart, and    -   a right atrial electrode positionable within the right atrium to        deliver cardiac therapy to or sense electrical activity of the        right atrium of the patient's heart;

a therapy delivery circuit operably coupled to the plurality ofelectrodes to deliver cardiac therapy to the patient's heart;

a sensing circuit operably coupled to the plurality of electrodes tosense electrical activity of the patient's heart; and

a controller comprising processing circuitry operably coupled to thetherapy delivery circuit and the sensing circuit, the controllerconfigured to:

-   -   deliver a left ventricular pace therapy using the        tissue-piercing electrode;    -   monitor effectiveness of left ventricular capture over a        plurality of cardiac cycles based on electrical activation        monitored using at least the tissue-piercing electrode;    -   determine that effective left ventricular capture is not        occurring based on the monitored of effectiveness of left        ventricular capture over the plurality of cardiac cycles; and    -   adjust left ventricular pacing in response to determination that        effective left ventricular capture is not occurring.

Various aspects disclosed herein may be combined in differentcombinations than the combinations specifically presented in thedescription and accompanying drawings. It should also be understoodthat, depending on the example, certain acts or events of any of theprocesses or methods described herein may be performed in a differentsequence, may be added, merged, or left out altogether (e.g., alldescribed acts or events may not be necessary to carry out thetechniques). In addition, while certain aspects of this disclosure aredescribed as performed by a single module or unit for purposes ofclarity, the techniques of this disclosure may be performed by acombination of units or modules associated with, for example, a medicaldevice.

In one or more examples, the described techniques may be implemented inhardware, software, firmware, or any combination thereof. If implementedin software, the functions may be stored as one or more instructions orcode on a computer-readable medium and executed by a hardware-basedprocessing unit. Computer-readable media may include non-transitorycomputer-readable media, which corresponds to a tangible medium such asdata storage media (e.g., RAM, ROM, EEPROM, flash memory, or any othermedium that can be used to store desired program code in the form ofinstructions or data structures and that can be accessed by a computer).

Instructions may be executed by one or more processors, such as one ormore digital signal processors (DSPs), general purpose microprocessors,application specific integrated circuits (ASICs), field programmablelogic arrays (FPGAs), or other equivalent integrated or discrete logiccircuitry. Accordingly, the term “processor” as used herein may refer toany of the foregoing structure or any other physical structure suitablefor implementation of the described techniques. Also, the techniquescould be fully implemented in one or more circuits or logic elements.

All references and publications cited herein are expressly incorporatedherein by reference in their entirety for all purposes, except to theextent any aspect incorporated directly contradicts this disclosure.

All scientific and technical terms used herein have meanings commonlyused in the art unless otherwise specified. The definitions providedherein are to facilitate understanding of certain terms used frequentlyherein and are not meant to limit the scope of the present disclosure.

Unless otherwise indicated, all numbers expressing feature sizes,amounts, and physical properties used in the specification and claimsmay be understood as being modified either by the term “exactly” or“about.” Accordingly, unless indicated to the contrary, the numericalparameters set forth in the foregoing specification and attached claimsare approximations that can vary depending upon the desired propertiessought to be obtained by those skilled in the art utilizing theteachings disclosed herein or, for example, within typical ranges ofexperimental error.

The recitation of numerical ranges by endpoints includes all numberssubsumed within that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3,3.80, 4, and 5) and any range within that range. Herein, the terms “upto” or “no greater than” a number (e.g., up to 50) includes the number(e.g., 50), and the term “no less than” a number (e.g., no less than 5)includes the number (e.g., 5).

The terms “coupled” or “connected” refer to elements being attached toeach other either directly (in direct contact with each other) orindirectly (having one or more elements between and attaching the twoelements). Either term may be modified by “operatively” and “operably,”which may be used interchangeably, to describe that the coupling orconnection is configured to allow the components to interact to carryout at least some functionality (for example, a first medical device maybe operatively coupled to another medical device to transmit informationin the form of data or to receive data therefrom).

Terms related to orientation, such as “top,” “bottom,” “side,” and“end,” are used to describe relative positions of components and are notmeant to limit the orientation of the embodiments contemplated. Forexample, an embodiment described as having a “top” and “bottom” alsoencompasses embodiments thereof rotated in various directions unless thecontent clearly dictates otherwise.

Reference to “one embodiment,” “an embodiment,” “certain embodiments,”or “some embodiments,” etc., means that a particular feature,configuration, composition, or characteristic described in connectionwith the embodiment is included in at least one embodiment of thedisclosure. Thus, the appearances of such phrases in various placesthroughout are not necessarily referring to the same embodiment of thedisclosure. Furthermore, the particular features, configurations,compositions, or characteristics may be combined in any suitable mannerin one or more embodiments.

As used in this specification and the appended claims, the singularforms “a,” “an,” and “the” encompass embodiments having pluralreferents, unless the content clearly dictates otherwise. As used inthis specification and the appended claims, the term “or” is generallyemployed in its sense including “and/or” unless the content clearlydictates otherwise.

As used herein, “have,” “having,” “include,” “including,” “comprise,”“comprising” or the like are used in their open-ended sense, andgenerally mean “including, but not limited to.” It will be understoodthat “consisting essentially of” “consisting of,” and the like aresubsumed in “comprising,” and the like.

The term “and/or” means one or all the listed elements or a combinationof at least two of the listed elements.

The phrases “at least one of,” “comprises at least one of,” and “one ormore of” followed by a list refers to any one of the items in the listand any combination of two or more items in the list.

What is claimed:
 1. An implantable medical device comprising: aplurality of electrodes comprising: a tissue-piercing electrodeimplantable from the triangle of Koch region of the right atrium throughthe right atrial endocardium and central fibrous body to deliver cardiactherapy to or sense electrical activity of the left ventricle in thebasal and/or septal region of the left ventricular myocardium of apatient's heart, and a right atrial electrode positionable within theright atrium to deliver the cardiac therapy to or sense electricalactivity of the right atrium of the patient's heart; a therapy deliverycircuit operably coupled to the plurality of electrodes to deliver thecardiac therapy to the patient's heart; a sensing circuit operablycoupled to the plurality of electrodes; and a controller comprisingprocessing circuitry operably coupled to the therapy delivery circuitand the sensing circuit, the controller configured to monitoreffectiveness of left ventricular capture by: operating the therapydelivery circuit to deliver a left ventricular pace using thetissue-piercing electrode; monitoring, via the sensing circuit,electrical activity of the left ventricle following the left ventricularpace using the tissue-piercing electrode; and determining effectivenessof left ventricular tissue capture of the left ventricular pace based onthe monitored electrical activity; and wherein monitoring electricalactivity of the left ventricle following the left ventricular pace usingthe tissue-piercing electrode comprises monitoring electrical activityof the left ventricle using the tissue-piercing electrode and the rightatrial electrode.
 2. The device of claim 1, wherein the controller isfurther configured to execute: monitoring effectiveness of leftventricular capture over a plurality of cardiac cycles; determining thateffective left ventricular capture is not occurring based on themonitored of effectiveness of left ventricular capture over theplurality of cardiac cycles; and adjusting left ventricular pacing inresponse to determining that effective left ventricular capture is notoccurring.
 3. The device of claim 2, wherein adjusting left ventricularpacing comprises adjusting one or both of a left ventricular pacingamplitude of the left ventricular pace and a delay between an atrialsense or pace and the left ventricular pace until effective leftventricular tissue capture of the left ventricular pace is determined.4. The device of claim 1, wherein determining effectiveness of leftventricular tissue capture of the left ventricular pace based on themonitored electrical activity comprises comparing a minimum negativedeflection within a selected time period following the left ventricularpace to a minimum threshold.
 5. The device of claim 1, whereindetermining effectiveness of left ventricular tissue capture of the leftventricular pace based on the monitored electrical activity comprisescomparing a time period between the left ventricular pace and a minimumnegative deflection to an interval threshold.
 6. The device of claim 1,wherein determining effectiveness of left ventricular tissue capture ofthe left ventricular pace based on the monitored electrical activitycomprises determining whether a minimum negative deflection of themonitored electrical activity occurs prior to a maximum positivedeflection of the monitored electrical activity.
 7. The device of claim1, wherein monitoring effectiveness of left ventricular capturecomprises periodically monitoring effectiveness of left ventricularcapture over a selected amount of cardiac cycles.
 8. A methodcomprising: implanting a tissue-piercing electrode in the triangle ofKoch region of the right atrium through the right atrial endocardium andcentral fibrous body to deliver cardiac therapy to or sense electricalactivity of the left ventricle in the basal and/or septal region of theleft ventricular myocardium of a patient's heart; providing a rightatrial electrode positionable within the right atrium to deliver cardiactherapy to or sense electrical activity of the right atrium of thepatient's heart; delivering a left ventricular pace using thetissue-piercing electrode; monitoring electrical activity of the leftventricle using the tissue-piercing electrode following the leftventricular pace; and determining effectiveness of left ventriculartissue capture of the left ventricular pace based on the monitoredelectrical activity; and wherein monitoring electrical activity of theleft ventricle following the left ventricular pace using thetissue-piercing electrode comprises monitoring electrical activity ofthe left ventricle using the tissue-piercing electrode and the rightatrial electrode.
 9. The method of claim 8, wherein the method furthercomprises: monitoring effectiveness of left ventricular capture over aplurality of cardiac cycles; determining that effective left ventricularcapture is not occurring based on the monitored effectiveness of leftventricular capture over the plurality of cardiac cycles; and adjustingleft ventricular pacing in response to determining that effective leftventricular capture is not occurring.
 10. The method of claim 9, whereinadjusting left ventricular pacing comprises adjusting one or both of aleft ventricular pacing amplitude of the left ventricular pace and adelay between an atrial sense or pace and the left ventricular paceuntil effective left ventricular tissue capture of the left ventricularpace is determined.
 11. The method of claim 8, wherein determiningeffectiveness of left ventricular tissue capture of the left ventricularpace based on the monitored electrical activity comprises comparing aminimum negative deflection within a selected time period following theleft ventricular pace to a minimum threshold.
 12. The method of claim 8,wherein determining effectiveness of left ventricular tissue capture ofthe left ventricular pace based on the monitored electrical activitycomprises comparing a time period between the left ventricular pace anda minimum negative deflection to an interval threshold.
 13. The methodof claim 8, wherein determining effectiveness of left ventricular tissuecapture of the left ventricular pace based on the monitored electricalactivity comprises determining whether a minimum negative deflection ofthe monitored electrical activity occurs prior to a maximum positivedeflection of the monitored electrical activity.
 14. The method of claim8, wherein the method further comprises issuing an alert if ineffectiveleft ventricular tissue capture is determined.
 15. The method of claim8, wherein monitoring effectiveness of left ventricular capturecomprises periodically monitoring effectiveness of left ventricularcapture over a selected amount of cardiac cycles.